bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of Aortic Diastolic Pressure Decay with Application to the Continuous Monitoring of Changes in Peripheral Vascular Resistance
Authors: BOURGEOIS MAURICE J. , GILBERT BARRY K. , DONALD DAVID E. , WOOD EARL H.
Published: June 2012

Large changes in stroke volume and peripheral vascular resistance were induced by varying the heart rate and by intra-aortically infusing acetylcholine or angiotensin II in six dogs with heart block and electromagnetic flowmeters chronically implanted around their ascending aortas. Changes in stroke volume, aortic and atrial pressures, and systemic resistance were monitored continuously for 3-6 hours under morphine-pentobarbital anesthesia. The characteristics of diastolic pressure decay at heart rates ranging from 60 beats/min to 200 beats/min and during transient periods of asystole were studied, especially with reference to the distortions caused by reflected pressure waves. The diastolic phase of pressure pulses recorded over a segment of the thoracic aorta several centimeters long centered about 4 cm cephalad to the dorsal insertion of the diaphragm could be closely approximated by a straight line on a semilogarithmic scale. Under the conditions of these experiments, changes in the slope of that line and of its reciprocal, the time constant, correlated well with concomitant variations in peripheral vascular resistance. This relationship appears to be of practical value for continuous monitoring of systemic resistance directly from the diastolic segments of pressure pulses recorded from the lower thoracic aorta.
Effect of Digitalis on Carotid Sinus Baroreceptor Activity
Authors: QUEST JOHN A. , GILLIS RICHARD A.
Published: June 2012

The effect of intracarotid injections of ouabain (25.0 µg) or acetylstrophanthidin (1.56 µg) on feline carotid sinus baroreceptors was evaluated using an isolated perfused carotid sinus preparation. The effects of the drugs on baroreceptor activity were determined by monitoring carotid sinus nerve activity and systemic arterial blood pressure. Administration of either drug to the isolated carotid sinus region altered the relationship between the change in carotid sinus pressure and the fall in systemic arterial blood pressure. Raising the carotid sinus pressure produced a greater depressor response when digitalis was present (-29.6 ± 3.8 mm Hg) than it did when digitalis was absent (-15.3 ± 2.6 mm Hg). Digitalis administration also resulted in a greater increase in carotid sinus nerve discharge when carotid sinus pressure was increased. At a constant carotid sinus pressure, digitalis increased the spontaneous firing of the carotid sinus nerve; the drug-induced augmentation in nerve firing was identical to that produced by raising carotid sinus pressure. These changes in baroreceptor activity in the presence of digitalis occurred without drug-induced changes in the pressure in the isolated carotid sinus region. The results demonstrate that the digitalis preparations studied can directly alter the sensitivity of baroreceptors and produce significant changes in carotid sinus nerve activity and cardiovascular function.
Impaired Autoregulation of Blood Flow and Glomerular Filtration Rate in the Isolated Dog Kidney Depleted of Renin
Authors: KALOYANIDES GEORGE J. , BASTRON ROBERT D. , DIBONA GERALD F.
Published: June 2012

The effect of renin depletion on autoregulation of renal blood flow and glomerular filtration rate was examined in an isolated perfused kidney preparation. Group 1 dogs received a normal-sodium diet, group 2 dogs received deoxycorticosterone acetate (DOCA) and a high-sodium diet, group 3 dogs received DOCA and a sodium-deficient diet, group 4 dogs received a high-sodium diet without DOCA, and dogs in groups 5 and 6 were treated just like dogs in groups 1 and 2, respectively. Renin release was stimulated by decreasing renal arterial pressure to 50 mm Hg. An increase in renal arterial pressure from 100 to 160 mm Hg was associated with an impaired autoregulatory response in kidneys from group 2 dogs and in two kidneys from group 4 dogs; these kidneys exhibited suppressed or absent renin release in response to a decrease in renal arterial pressure. A separate group of experiments demonstrated that DOCA plus a high-sodium diet completely depleted the kidney of renin stores, indicating that decreased renin secretion reflected depletion of renal renin content. Infusing angiotensin II (0.22 ± 0.06 µg/min) into the renal artery of group 2 kidneys did not normalize the autoregulatory response. A decrease in renal arterial pressure from 150 to 50 mm Hg was associated with impaired autoregulation of glomerular filtration rate and renal blood flow in kidneys from group 6 dogs; renin secretion was undetectable in these kidneys. All kidneys from groups 1, 3, and 5 and the remaining six kidneys from group 4 exhibited a normal autoregulatory response and normal renin release. In groups 1-3, zonal blood flow was measured using the radiolabeled microsphere technique. Only in group 2 did a significant redistribution of fractional blood flow from the inner to the outer cortex occur. These experiments demonstrate that renin depletion impairs the capacity of the kidney to autoregulate blood flow and glomerular filtration rate; thus the data are consistent with the hypothesis that the renin-angiotensin system participates in the autoregulatory response.
Recovery from Cardiac Bypass and Elective Cardiac Arrest
Authors: HEARSE DAVID J. , STEWART DAVID A. , CHAIN ERNST B.
Published: June 2012

Isolated perfused working rat hearts were subjected to elective cardiac arrest for 20 or 30 minutes. Various methods of arrest, either singly or in combination and with or without coronary perfusion, were studied. The functional recovery of the heart following the termination of arrest was related to the concentration of adenosine triphosphate (ATP) and creatine phosphate in the myocardium at the end of the period of arrest. In turn, these concentrations depended on the method used to induce arrest. Normothermic ischemic arrest or electrical fibrillation led to a marked reduction in high-energy phosphates and a poor functional recovery. In contrast, coronary perfusion with hypothermic solutions or solutions containing high concentrations of potassium induced arrest without depleting ATP or creatine phosphate. These procedures conferred considerable protection on the myocardium and thus permitted good recovery. The energy status and the recovery associated with ischemic arrest were improved by combining the ischemia with potassium-induced arrest, intermittent coronary perfusion, or hypothermia. In the latter instance, a time- and temperature-dependent relationship was demonstrated. The results stress the importance of maintaining ATP and creatine phosphate levels during arrest; such maintenance requires the provision of a continuous supply of oxygen and nutrient, which may perhaps be best achieved by ensuring continuous and adequate coronary perfusion.
Increased Metabolic Turnover Rate and Transcapillary Escape Rate of Albumin in Essential Hypertension
Authors: PARVING HANS-HENRIK , ROSSING NIELS , JENSEN HENRIK AE.
Published: June 2012

The metabolic turnover rate and the transcapillary escape rate of albumin were studied using
131
I-labeled human albumin in nine untreated subjects suffering from essential hypertension. The average mean arterial blood pressure of these subjects was 162/109 mm Hg; seven subjects had grade I-II funduscopic changes. Plasma albumin concentration was normal, but plasma volume was reduced (
P
< 0.05) in these subjects. Thus, the previously reported moderate decrease in the intravascular albumin mass of hypertensive subjects was confirmed; the average value for intravascular albumin mass in the present study was 62.8 g/m2 surface area compared with a normal value of 70.6 g/m
2
(-11%,
P
< 0.05). A surprising finding was a marked enhancement of albumin metabolic rate in essential hypertension. The fraction of intravascular albumin mass metabolized per 24-hour period was on the average 14.4% compared with a normal value of 8.4% (+72%,
P
< 0.001). The rate of synthesis was 9.1 g/24 hours m
-2
compared with a normal value of 5.9 g/24 hours m
-2
(+54%,
P
< 0.001). Total body albumin mass was decreased proportionally to intravascular albumin mass. Confirming a previous observation, we found an increase in the transcapillary escape rate of albumin (fraction of intravascular mass passing to the extravascular space per unit time) from a normal average of 5.6%/hour to 7.5%/hour (+34%,
P
< 0.001). There was a statistically significant positive correlation between the transcapillary escape rate of albumin and blood pressure (
P
< 0.05). These findings can best be explained by increased filtration due to the high arterial blood pressure. There was also a positive correlation between the transcapillary escape rate and the fractional catabolic rate of albumin (
P
< 0.05). This finding supports the concept that albumin is catabolized in connection with its permeation through the capillary endothelium.
Gastrointestinal and Mesenteric Hemodynamic Patterns in Neurogenic Hypertensive Rabbits
Authors: ALEXANDER NATALIE , DeQUATTRO VINCENT
Published: June 2012

Patterns of blood flow and vascular resistance in the component tissues of the splanchnic region of sinoaortic denervated (SAD) hypertensive rabbits were compared with those of normotensive sham-operated rabbits using previously described methods. SAD rabbits with high total splanchnic resistance showed significant elevations in resistance in all parts of the gastrointestinal tract and mesentery, but the magnitude of the changes compared with values for sham-operated rabbits varied from one area to another, ranging from increases of 34% in the cecum-appendix to 77% in the stomach and jejunum. Blood flow was reduced 22-42% in some areas and less in others. An aboral gradient of mean blood flow was found between and within the small and large intestines in both groups. Intestinal flow pattern differences were found in individual rabbits. We concluded that activation of the sympathetic nervous system by sinoaortic denervation exerted a variable, unpredictable degree of vasoconstrictor tone on different parts of the splanchnic bed which reflected the net result of vascular smooth muscle response to neurogenic and local regulatory factors.
Evidence in Support of Hypoxia but Against High Potassium and Hyperosmolarity as Possible Mediators of Sustained Vasodilation in Rabbit Cardiac and Skeletal Muscle
Authors: Gellai Miklos , Detar Reed
Published: June 2012

The vasoactive properties of hypoxia, elevated extracellular potassium concentration ([K]
o
), and hyperosmolarity were studied in helical strip preparations of small coronary and deep femoral arteries (260-700 µm, o.d.) equilibrated in a physiological salt solution with an oxygen tension (Po
2
) of 100 mm Hg, [K]
o
of 3.18 mM, and an osmolarity of 304 milliosmoles/liter. Increasing [K]
o
(2-6 mM) or osmolarity (30-50 milliosmoles/liter) produced relaxation of resting tension in 50% of the coronary strips but had no effect on resting tension in deep femoral strips. Sustained increments in [K]
o
or osmolarity produced concentration-dependent, transient relaxation of aganist-induced contractile tension in both coronary and deep femoral arterial strips: a potassium increment of 4 mM produced 40% relaxation with 100% recovery within 5-6 minutes, an osmotic increment of 30 milliosmoles/liter caused 20-40% relaxation with 100% recovery within 15-60 minutes, and simultaneous potassium (4 mM) and osmotic (30 milliosmoles/liter) increments produced 85-95% relaxation with 100% recovery within 10-15 minutes. Decreasing Po
2
from 100 mm Hg to 10 mm Hg resulted in a sustained 35-40% fall in agonist-induced contractile tension. Although a nonspecific additive interaction was observed during a simultaneous change to high [K]
o
, hyperosmolarity, and hypoxia, for any given level of vascular tone hypoxia had little or no effect on the degree or the duration of the tension relaxation-recovery sequence produced by elevated [K]
o
, hyperosmolarity, or both. Therefore, it is proposed that hypoxia is the only one of these three factors that, by a direct interaction with vascular smooth muscle cells, can contribute to sustained vasodilation of small arteries in rabbit cardiac or skeletal muscle.
Reactive Hyperemia in the Dog Heart
Authors: Eikens Eduards , L.Wilcken David E.
Published: June 2012

With electromagnetic flow transducers and pneumatic cuff occluders on the circumflex branch of the left coronary artery in conscious and in anesthetized dogs, we examined the effects of both a temporary reduction in postocclusion hyperemia and one- and two-cardiac cycle occlusions of the artery on the size and the duration of the hyperemic response. After release of 8-second occlusions, flow was prevented from rising to more than 10-20% above the preocclusion value for the expected duration of the hyperemia. Peripheral coronary arterial pressure measurements established that this maneuver produced a pressure gradient. Temporary restriction of arterial inflow markedly reduced the percent repayment of the flow deficit from 618 ± 34± to 213 ± 17% (mean ± SE) and moderately prolonged the duration of the response from 95 ± 4 seconds to 129 ± 5 seconds (
P
< 0.0005 for both). In conscious dogs, the mean percent repayment after a one-cycle (0.7-second) occlusion was 227%. Much larger and longer-lasting responses were obtained with one-cycle (0.4-second) occlusions in anesthetized dogs in which heart rate and blood pressure were considerably higher. Since restricting arterial inflow resulted in a large reduction in reactive hyperemia with only a small increase in its duration, local mechanisms acting in the interstitial space and possibly in the vascular smooth muscle may be relatively more important for the hyperemia that occurs after short occlusions than is the myocardial release of freely diffusible metabolites that are removed by the blood stream. The results with one- and two-cycle occlusions suggest that myogenic responses contribute to the hyperemia, since it is unlikely that such brief occlusions produce myocardial hypoxia under resting conditions.
Canine Lipoproteins and Atherosclerosis
Authors: MAHLEY ROBERT W. , WEISGRABER KARL H.
Published: June 2012

Canine plasma lipoproteins were fractionated into four distinct classes by ultracentrifugation combined with Geon-Pevikon block electrophoresis and characterized with respect to physical and chemical properties. The distribution of plasma lipids and lipoproteins was quite unlike that in man, the dog having approximately five to six times as much high density as lower density lipoproteins. Despite the marked difference in distribution, human lipoprotein equivalents were present. Very low density lipoproteins (VLDL) isolated at density less than 1.006 g/ml were triglyceride-rich particles ranging in size from 260 to 900 Å in diameter. The density range from 1.006 to 1.063 g/ml contained two classes of lipoproteins: one closely resembled aolow density lipoprotein (LDL) with β mobility and a particle size of approximately 200 Å and the other (called HDL
1
) was closely related to the high density lipoproteins with respect to immunochemical reactivity, electrophoretic mobility, and apoprotein content. The HDL
1
particles ranged in size from 100 to 350 Å in diameter and appeared to be unlike any of the commonly described human lipoproteins. High density lipoproteins called HDL
2
isolated in the density range from 1.087 to 1.21 g/ml were protein-rich particles ranging in size from 55 to 85 Å. The apolipoprotein patterns of VLDL, LDL, and HDL
2
on polyacrylamide gel electrophoresis were similar to those of the corresponding lipoproteins of man.
Urinary Kallikrein Excretion in Hypertensive Man
Authors: MARGOLIUS HARRY S. , HORWITZ DAVID , PISANO JOHN J. , KEISER HARRY R.
Published: June 2012

Urinary kallikrein excretion was measured by a radiochemical esterolytic assay in patients with essential hypertension or primary aldosteronism. Patients with essential hypertension excreted significantly less (
P
< 0.001) kallikrein than did normal subjects when they were allowed an ad libitum sodium intake or given 259 mEq sodium/day. When sodium intake was changed from ad libitum to 9 mEq/day, kallikrein excretion increased in the majority of patients with essential hypertension, but it remained significantly less (
P
< 0.001) than that in normal subjects; however, aldosterone excretion was similar in both groups. Fludrocortisone, 0.5 mg/day for 10 days, increased kallikrein excretion in three patients with essential hypertension. In patients with primary aldosteronism, mean kallikrein excretion was sevenfold higher (
P
< 0.001) than that in patients with essential hypertension; kallikrein excretion remained unchanged when dietary sodium was altered, but it was decreased by treatment with spironolactone. Mean kallikrein excretion in patients with primary aldosteronism was also significantly higher (
P
< 0.001) than that in a normotensive control population. The results show that kallikrein excretion reflects the effective level of circulating sodium-retaining steroid in patients with primary aldosteronism but suggest that it is relatively unresponsive to endogenous sodium-retaining steroid in patients with essential hypertension. The data raise the possibility that the kallikrein-kinin system is of pathogenetic significance in human hypertensive disease.
Vascular endothelium-leukocyte interaction; sticking shear force in venules.
Authors: Schmid-Schoenbein G W , Fung Y C , Zweifach B W
Published: June 2012

To determine the shear force acting on a white blood cell sticking to the endothelium of a blood vessel, the flow field about a single white blood cell in a venule was determined by hign-speed motion picture photomicrography. The force acting on the white blood cell was then calculated according to the principles of fluid mechanics. In this paper, the calculation was made using an experimentally determined dimensionless shear force coefficient obtained from a kinematically and dynamically similar model. The large physical model of the hemodynamic system could be easily instrumented, and the shear force acting on the model cell and the flow field around it were measured. The data were then used to calculate a shear force coefficient. On the basis of dynamic similarity, this shear force coefficient was applied to the white blood cell in the venule. The shear force coefficient was strongly influenced by the hematocrit, so in vivo hematocrits were measured from electron micrographs. It was found that in the venules of the rabbit omentum a white blood cell sticking to the endothelial wall was subjected to a shear force in the range of 4 times 10--5 dynes to 234 times 10--5 dynes; the exact value depended on the size and motion of the white blood cell, the size of the blood vessel, the velocity of the blood flow, and the local hematocrit, which varied between 20% and 40% in venules of about 40 mum in diameter. The contact area between the white blood cell and the endothelial cell was estimated, and the shear stress was found to range between 50 dynes/cm-2 and 1060 dynes/cm-2. The normal stress of interaction between the white blood cell and the endothelium had a maximum value that was of the same order of magnitude as the shear stress. The accumulated relative error of the experimental procedure was about 49%. The instantaneous shear force was a random function of time because of random fluctuations of the hematocrit.
Anoxia-induced release of prostaglandins in rabbit isolated hearts.
Authors: Block A J , Feinberg H , Herbaczynska-Cedro K , Vane J R
Published: June 2012

We investigated the relationship between prostaglandin release and the coronary vasodilation evoked by anoxia. Isolated rabbit hearts were perfused via the aorta with Krebs-Ringer's solution. The coronary effluent was bioassayed continuously in terms of prostaglandin E2 for prostaglandinlike substance which was present (at less than 1 ng/ml) in 60 of 66 hearts. This basal release was abolished by the prostaglandin synthetase inhibitor, indomethacin (1-2 mug/ml), a result which adds further to the identity of the prostaglandinlike substance as a prostaglandin. Anoxia increased coronary flow sometimes by 100% and evoked prostaglandin release shortly thereafter. Ablolition of prostaglandin synthesis by indomethacin pretreatment did not affect nor did infusion of exogenous prostaglandin mimic the anoxia-induced flow increment; thus, we conclude that prostaglandin release cannot account for the anoxia-induced vasodilator response. Furthermore, the failure of indomethacin to alter resting coronary blood flow suggests that a local prostaglandin release is not responsible for either the maintenance or the modulation of coronary flow in this preparation.
Arterial fibrous proteins in cynomolgus monkeys after atherogenic and regression diets.
Authors: Armstrong M L , Megan M B
Published: June 2012

Fibrous proteins were measured in five arterial beds in adult cynomolgus monkeys after administration of atherogenic and regression regimens. Atherosclerosis was induced by feeding the monkeys a hypercholesterolemic diet containing 1.2% cholesterol for 17 months. A low-fat, cholesterol-free regression diet was then given for 60 days, 200 days, and 20 months. In atherosclerosis, collagen concentration (mg/g dry weight) and collagen content (mg/cm length of artery) both increased. At 200 days of regression the collagen concentration, but not the collagen content, was higher than it was in atherosclerosis. In late regression (20 months), the collagen content was lower than it was in atherosclerosis, although in the five arterial beds considered together the collagen concentration was not significantly lower. Both the elastin concentration and the elastin content rose in atherosclerosis and decreased in regression. These mass data suggest that fibrous proteins are lost from the arterial wall during a regression regimen. Correlative evidence suggests that younger intimal fibers may be chiefly susceptible to fibrolytic activity, leaving dense intimal scars characteristic of regressed arteries.
Catecholamine-dependent cyclic adenosine monophosphate and renin in the dog kidney.
Authors: Beck N , Kim K S , Davies B B
Published: June 2012

Lithium inhibits the catecholamine-dependent cyclic adenosine monophosphate (AMP) generation in the kidney but not the hemodynamic effects of beta-adrenergic stimulation. Therefore, the possible role of catecholamine-dependent cyclic AMP in the release of renin was investigated in lithium-treated dogs both in vivo and vitro. Lithium therapy had no measurable effect on the increase in plasma renin activity induced by an injection of isoproterenol (2.6 plus and minus 1.2 (SE) ng/hour in control dogs vs. 3.0 plus and minus 1.2 ng/hour in lithium-treated dogs, P greater than 0.05). However, lithium inhibited the isoproterenol-induced increase in urinary excretion of cyclic AMP in vivo (791 plus and minus 199 pmoles/min in control dogs vs. 123 plus and minus 129 pmoles/min in lithium-treated dogs, P less than 0.05) and the increase in cyclic AMP concentration in renal tissue in vitro (4.50 plus and minus 0.15 pmoles/ng wet tissue in control dogs vs. 0.34 plus and minus 0.26 pmoles/mg in lithium-treated dogs, P less than 0.01). The finding that, in the lithium-treated dogs, isoproternol increased plasma renin activity but not cyclic AMP generation in the kidney suggests that the increase in plasma renin activity observed after an injection of isoproterenol is probably not mediated through the beta-adrenergic stimulus-dependent cyclic AMP system in the kidney.
Magnetic determination of the relationship between the S-T segment shift and the injury current produced by coronary artery occlusion.
Authors: Cohen D , Kaufman L A
Published: June 2012

Both the S-T segment shift and the injury current were measured using the direct-current magnetocardiogram (d-c MCG) in seven dogs undergoing coronary artery occlusion. The purpose of the measurements was to clarify the origin of the S-T shift in acute ischemia and infarction. Previous measurements, consisting of d-c electrograms recorded from the exposed epicardial surface in situ, are partially inconsistent; also, they are not necessarily representative of the surface electrocardiogram (ECG), which sums broadly over the myocardium. The d-c MCG allows steady myocardial currents in the intact torso to the measured externally; because the d-c MCG sums broadly over these currents, conclusions drawn from it are applicable to the ECG. Coronary artery occlusion was produced by inflating a tube which, about 1 week earlier, had been surgically installed around the artery and exteriorized. During occlusions carried out in the MIT magnetically shielded room, a sensitive magnetometer recorded the d-c MCG at various locations around the torso. Within 20 seconds after occlusion, equal and opposite S-T segment and base-line (d-c) shifts appeared on the d-c MCG; these shifts were maintained for at least 15 minutes, after which they slowly decreased. Therefore, during the acute ischemia produced by these occlusions, the S-T shift is a secondary result of a primary injury current that is interrupted during the S-T interval.
Impairment of autonomically mediated heart rate control in patients with cardiac dysfunction.
Authors: Goldstein R E , Beiser G D , Stampfer M , Epstein S E
Published: June 2012

Patients with cardiac disorders have defective parasympathetic control of heart rate. To evaluate the possibility of similar changes in sympathetic control of heart rate, we compared reflex chronotropic responses to 80 degree upright tilt and nitroglycerin-induced hypotension in 31 cardiac patients and 7 normal individuals before and after partial parasympathetic blockade with atropine. Tilting revealed an attenuation of the normal heart rate increase in patients; the magnitude of this defect was greatest in patients with more severe symptoms (class III) and evidence of left ventricular dysfunction (the heart rate increase averaged 25 plus or minus 3 beats/min in normal subjects, 12 plus or minus 2 beats/min in class I-II patients, and 7 plus or minus 1 beats/min in class III patients). Class III symptoms due to mechanical causes (mitral stenosis), however, were not associated with this defect. A marked reduction in heart rate rise with hypotension was seen only in those class III patients without mitral stenosis (0.4 plus or minus 0.1 beats min-minus 1 mm Hg-minus 1 vs. 3.0 plus or minus 0.5 beats min-minus 1 mm Hg-minus 1 in normal subjects). This abnormality also persisted after atropine administration, thus confirming a defect in the sympathetic as well as the parasympathetic component of baroreceptor-mediated reflex heart rate control in patients with cardiac dysfunction. Infusions of isoproterenol produced equivalent rises in heart rate in patients and normal individuals, excluding a reduction in beta-receptor responsiveness as a cause of impaired sympathetic influence. Norepinephrine depletion, however, is a well-recognized concomitant of cardiac failure. It is possible that the reduction in sympathetically mediated heart rate responses results in part from depletion of the sympathetic neurotransmitter.
Intimal ultrastructure of human umbilical arteries. Observations on arteries from newborn children of smoking and nonsmoking mothers.
Authors: Asmussen I , Kjeldsen K
Published: June 2012

The umbilical artery was chosen as a possible model for evaluating the vascular injury provoked by tobacco smoking in humans. Cords from newborn children delivered by 15 nonsmoking and 13 smoking mothers were studied in the transmission and the scanning electron microscope. Pronounced intimal changes were seen in the arteries from smoking mothers; the most important findings were degenerative changes of the endothelium such as swelling, blebbing, contraction, and subsequent opening of the endothelial junctions with formation of subendothelial edema. Other observations included dilation of the endoplasmic reticulum in the endothelium and reparative changes such as a considerable widening of the basement membrane. Since similar changes can be induced in arteries of animals by exposure to carbon monoxide or perfusion with nicotine, we conclude that the present study supports the concept that tobacco smoking is harmful to the vascular endothelium. This study also contributes to an understanding of the mechanism through which vascular injury is provoked in heavy smokers.
Hypertension, transmural pressure, and vascular smooth muscle response in rats.
Authors: Hansen T R , Bohr D F
Published: June 2012

The effect of transmural pressure on the responsiveness of vascular smooth muscle was studied using rats with chronic occlusion of one external iliac artery. The arterial pressure in the occluded leg was reduced to approximately half of that in the contralateral unoccluded leg. Helical strips from the low- and high-pressure femoral arteries of spontaneously hypertensive rats and rats with deoxycorticosterone acetate-induced (DOCA) hypertension were compared with corresponding tissues from normotensive controls. The sensitivity of both low- and high-pressure artery strips from the spontaneously hypertensive rat was greater than that of controls when strontium or lanthanum was used as the agonist. The sensitivity of strips from both low- and high-pressure arteries from the DOCA-hypertensive rat was greater than that of controls when potassium, epinephrine, or calcium was the agonist. There was no difference in sensitivity between strips from the low- and high-pressure arteries in any group of rats. Maximum contractile force (contractility) was reduced in femoral artery strips from both legs of all hypertensive rats. The KCl-induced contraction of vascular smooth muscle from both femoral arteries of either form of hypertensive rat was not as readily depressed by high calcium concentrations as was that from the normotensive rat. Changes in sensitivity and contractility associated with hypertension could not be reversed by lowering blood pressure in one leg of a spontaneously hypertensive rat or prevented by protecting one leg from high pressure prior to the induction of DOCA hypertension. The altered sensitivity and contractility of arterial strips in these models of hypertension are not, then, secondary to the increase in wall stress.
Modulation by prostaglandins of adrenergic transmission in the isolated perfused rabbit and rat kidney.
Authors: Malik K U , McGiff J C
Published: June 2012

In the isolated perfused rabbit kidney prostaglandins (PGS) E1 (0.02-0-1 ng/ml), E2 (0.02-0.1 ng/ml), and A2 (1-5 ng/ml) inhibited the vasoconstrictor responses to sympathetic nerve stimulation by 21-44%, 31-39%, and 20-23%, respectively, without alerting those to injected norepinephrine. In contrast, in the rat kidney PGE1 (0.5 ng/ml), PGE2 (0.5 ng/ml), and PGA2 (5 ng/ml) enhanced the vasoconstrictor responses to sympathetic nerve stimulation by 41%, 27%, and 11%, respectively; the equiconstrictor responses to injected norepinephrine remained unaltered. Higher concentrations of these agents produced vasodilation in the rabbit kidney and vasoconstriction in the rat kidney. In both species PGF2alpha produced vasoconstriction and enhanced the response to both adrenergic stumuli. In the rabbit kidney inhibitors of PG synthesis augmented the responses to sympathetic nerve stimulation without altering those to injected norepinephrine, whereas in the rat kidney inhibition of the responses to both adrenergic stimuli occurred. Arachidonic acid inhibited the vasoconstrictor responses to sympathetic nerve stimulation in the rabbit kidney, but in the rat kidney it caused augmentation of these responses. Since these effects of arachidonic acid were reduced by indomethacin, they appear to be mediated through the acid's conversion to PGS. We conclude that PGS of the E series modulate adrenergic transmission in the kidney and that their modulatory actions are species dependent.
A new method of measuring propagation coefficients and characteristic impedance in blood vessels.
Authors: Milnor W R , Nichols W W
Published: June 2012

True propagation coefficients of pulse wave harmonics in an artery can be determined in vivo by measuring pulsatile blood pressure and flow at each of two points along the length of the vessel. These coefficients, which are complex numbers that describe the attenuation and the phase shift imposed on a traveling wave, are independent of the reflected waves in the circulation and thus provide information about the viscoelastic state and other properties of an artery. The equations involved are implicit in standard transmission-line theory, but they have not previously been applied in this particular way to blood vessels. The femoral artery, exposed in situ, was studied in 11 anesthetized dogs. At 1.5 Hz, true attenuation constants averaged 0.0151 nepers/cm, and true phase constants averaged 0.0155 radians/cm. As frequency increased, the apparent phase velocity of flow, in contrast, was relatively low at the first harmonic and rose as frequency increased. True phase velocities lay between the apparent pressure and flow values. Characteristic impedance at 1.5 Hz had an average modulus of 1.76 times 10-4 dyne sec/cm5 and a phase of minus 0.31 radians. The modulus diminished as frequency increased, and the phase became less negative. These results show that true phase constants and characteristic impedances determined by this method are consistent with data reported by others and provide information not previously available about flow wave propagation.
Cardiovascular regulation by central adrenergic mechanisms and its alteration by hypotensive drugs.
Authors: Haeusler G
Published: June 2012

Electrical stimulation of the posterior hypothalamus is followed by an immediate increase in sympathetic nerve activity and rise in blood pressure. Destruction of hypothalamic adrenergic structures by local unilateral injection of 6-hydroxydopamine into the posterior hypothalamus reduced the blood pressure rise in response to stimulation of the lesioned side. This and numerous other findings indicate an involvement of central adrenergic neurons in the mediation of an increase of sympathetic nerve activity caused by hypothalamic stimulation. However, central adrenergic neurons do not seem to be an integral part of the sympathoexcitatory pathways originating in the posterior hypothalamus but rather facilitate their activation: after almost complete norepinephrine depletion produced by combined treatment with reserpine and alpha-methl-p-tyrosine, hypothalamic stimulation was still followed by an increase in spontaneous sympathetic nerve activity. Stimulation of an alpha-adrenoceptive site, probably located in the lower brain stem, mimics an activation of the baroreceptor reflex. The hypotensive drug, clonidine, stimulates this alpha-adrenoceptive site. In low doses clonidine facilitates the activation of the reflex, and in high doses this drug induces a state which closely resembles a pronounced activation of the reflex. Experiments following depletion of norepinephrine suggest that the central part of the baroreceptor reflex arc does not contain adrenergic neurons. However, these findings are compatible with the view that some neurons within the reflex arc are supplied with alpha-adrenoceptors. For the present it cannot be stated with certainty whether these alpha-adrenoceptors possess an innervation by adrenergic neurons projecting onto the reflex arc. In favor of such an innervation are the obsevations that alpha-methyldopa has its site of action in the lower brain stem and that the integrity of central adrenergic neurons is essential for its hypotensive effect. It seems that two central adrenergic systems exist with opposing effects on cardiovascular control. These are an excitatory hypothalamic and an inhibitory bulbar adrenergic system. Partial destruction of central adrenergic neurons by intraventricularly injected 6-hydroxydopamine prevents the development of DOCA/NaCl, renal, and neurogenic hypertension and alters the pattern of blood pressure rise in spontaneously hypertensive rats. Impairment of central adrenergic function or imbalance of the two central adrenergic mechanisms may represent a trigger mechanism for the initiation of hypertension.
Inhibition of coronary blood flow by a vascular waterfall mechanism.
Authors: Downey J M , Kirk E S
Published: June 2012

The mechanism whereby systole inhibits coronary blood flow was examined. A branch of the left coronary artery was maximally dilated with an adenosine infusion, and the pressure-flow relationship was obtained for beating and arrested states. The pressure-flow curve for the arrested state was shifted toward higher pressures and in the range of pressures above peak ventricular pressure was linear and parallel to that for the arrested state. Below this range the curve for the beating state converged toward that for the arrested state and was convex to the pressure axis. These results were compared with a model of the coronary vasculature that consisted of numerous parallel channels, each responding to local intramyocardial pressure by forming vascular waterfalls. When intramyocardial pressure in the model was assigned values from zero at the epicardium to peak ventricular pressure at the endocardium, pressure-flow curves similar to the experimental ones resulted. Thus, we conclude that systole inhibits coronary perfusion by the formation of vascular waterfalls and that the intramyocardial pressures responsible for this inhibition do not significantly exceed peak ventricular pressure.
Mesenteric hemodynamics in early experimental renal hypertension in dogs.
Authors: Simon G , Pamnani M B , Dunkel J F , Overbeck H W
Published: June 2012

To investigate mesenteric hemodynamics in early perinephritic hypertension, we measured blood flows and intravascular pressures in innvervated, collateral-free, naturally perfused loops of ileum in 50 male mongrel dogs anesthetized with sodium pentobarbital. In addition, we studied venous pressure-volume relationships in temporarily occluded segments of mesenteric veins in vivo and in excised segments of mesenteric veins in vitro. In 10 dogs (group H-1), one kidney was wrapped in silk 11 days before study; in 15 other dogs (group H-2), one kidney was wrapped 4 weeks before study and the other was removed 2 weeks before study. Twenty-five additional dogs were prepared as normotensive controls: in 10 one kidney was sham-wrapped (group C-1), and in 15 one kidney was sham-wrapped and the other was removed (group C-2). A significant rise in mean arterial blood pressure occurred in groups H-1 and H-2. Compared to controls, (1) ileal blood flow in the hypertensive dogs (H-1 plus H-2) was increased by 17% (P smaller than 0.05), (2) calculated ileal vascular resistances (total and segmental) were unchanged (P smaller than 0.05), and (3) in vivo and in vitro mesenteric vein pressure-volume curves of H-2 (but not of H-1) hypertensive dogs were shifted in the direction of the pressure axis (P smaller than 0.05). These data suggest that in the early stages of perinephritic hypertension in dogs (1) ileal blood flow is increased. (2) ileal vascular resistance is not elevated, and (3) mesenteric venous compliance is reduced. Analysis of the venous pressure-volume curves suggests that the decreased venous compliance is attributable to factors other than smooth muscle contraction.
Effects of norepinephrine and angiotensin II on the determinants of glomerular ultrafiltration and proximal tubule fluid reabsorption in the rat.
Authors: Myers B D , Deen W M , Brenner B M
Published: June 2012

In 26 Wistar rats with surface glomeruli, the determinants of glomerular ultrafiltration and peritubular capillary uptake of proximal reabsorbate were studied before and during intravenous infusions of norepinephrine or angiotensin II. Regardless of whether renal perfusion pressure (AP) was permitted to increase, both hormones produced elevations in single nephron filtration fraction due to declines in glomerular plasma flow with little change in nephron glomerular filtration rate. The resulting large increases in the efferent arteriolar oncotic pressure, piE, were accompanied by equivalent increases in the mean glomerular transcapillary hydraulic pressure difference, deltaP. Equality of piE and deltaP, denoting filtration pressure equilibrium, obtained before and during infusion of either hormone. Por both hormones, when elevations in AP were allowed, marked and roughly proportional increases in the resistance to blood flow through single afferent and efferent arterioles occurred, whereas when increases in AP were prevented by partial aortic constriction increases in resistance were confined primarily to the efferent arteriole. Tespite the marked increases in piE, absolute rates of proximal tubule fluid reabsorption, on the average, were unchanged by these hormones due to the opposing effects of marked decreases in efferent arteriolar plasma flow rate and, to a lesser extent, increases in peritubular capillary hydraulic pressure.
Reflex heart rate control via specific aortic nerve afferents in the rabbit.
Authors: Kardon M B , Peterson D F , Bishop V S
Published: June 2012

Reflex bradycardia was elicited in rabbits via repetitive electrical stimulation of the central end of the sectioned left aortic nerve. Supramaximal stimulation produced a 16.9 plus or minus 1.3% (SE) increase in the R-R interval when vagal and sympathetic efferent pathways were intact. Reducing the stimulation voltage allowed selective stimulation of the myelinated (A) fibers, and polarizing electrodes placed central to the stimulus site permitted A fiber blockade and selective stimulation of the unmyelinated (C) fibers. When afferent A fibers were selectively stimulated, 64% of the maximum response was obtained; selective C fiber activation elicited 63% of the maximum observed response. Selective stimulation of A or C fibers after either vagotomy or stellectomy indicated that A fiber afferents elicit heart rate responses via both vagal and sympathetic efferents, whereas C fiber afferent information is mediated predominantly via vagal efferents. This afferent-efferent specificity of the aortic baroreceptor pathways suggests baroreceptor mechanisms normally used to modulate heart rate. Small increments in blood pressure would activate low-threshold A fibers and result in reciprocal changes in vagal and sympathetic efferent activity. More substantial increases in blood pressure would activate afferent C fibers and produce additional heart rate effects via vagal efferents.
Control of aldosterone secretion in the spontaneously hypertensive rat.
Authors: Freeman R H , Davis J O , Aharon N V , Ulick S , Weinberger M H
Published: June 2012

Adrenal secretion rates of aldosterone, corticosterone, and deoxycorticosterone were studied sequentially in the spontaneously hypertensive rat and the normotensive Kyoto Wistar rat. Steroid secretion was studied at three different ages: 7-8, 11-13, and 22-25 weeks. Also, peripheral plasma levels of aldosterone and plasma renin activity were determined in both the spontaneously hypertensive and the normotensive rats at 7-8 weeks of age. Aldosterone secretion was elevated markedly in dexamethasone-morphine-treated spontaneously hypertensive rats at both 7-8 and 11-13 weeks of age but was not significantly different from control in 22-25-week-old spontaneously hypertensive rats. No statistically significant differences in corticosterone or deoxycorticosterone secretion rates were observed between the spontaneously hypertensive rats and the normotensive Kyoto Wistar controls; however, the data suggested that dexamethasone did not suppress adrenocorticotropic hormone in the 7-8- and 11-13-week-old spontaneously hypertensive rats to the same extent that it did in the normotensive Kyoto Wistar rats. Therefore, aldosterone secretion was reexamined in acutely hypophysectomized 7-8-week-old rats to eliminate completely the influence of the anterior pituitary; no differences in aldosterone, corticosterone, or deoxycorticosterone secretion rates were observed between hypophysectomized spontaneously hypertensive rats and normotensive Kyoto Wistar rats. Moreover, aldosterone secretion in the hypophysectomized 7-8-week-old spontaneously hypertensive rats was reduced markedly compared with that in the intact 7-8-week old spontaneously hypertensive rats, thus confirming the importance of the pituitary in these animals. Determinations of peripheral plasma aldosterone concentration and plasma renin activity in unstressed 7-8-week-old spontaneously hypertensive and normotensive rats revealed that both parameters were depressed significantly in the spontaneously hypertensive rats. Thus, the present data indicate that the renin-angiotensin-aldosterone system is suppressed in the spontaneously hypertensive rat but do not suggest that the system is critically involved in the hypertensive process in these animals
Effects of potassium ion on the microcirculation of the hamster.
Authors: Duling B R
Published: June 2012

The vasoactive properties of potassium were assessed in the microcirculation of the hamster cremaster muscle and the muscular and epithelial portions of the hamster cheek pouch. Tissues were transilluminated and suffused with a physiological salt solution whose potassium concentration varied from 0 to 20 mM. Vessel diameters were measured and normalized as a percent of the control diameter (+/- SE) observed during exposure to 4.7 mM K+. Altering the potassium concentration in the suffusion solution caused a transient vascular response. The peak changes in the vascular diameter of the arterioles supplying striated muscle varied directly with the suffusion solution potassium concentration from a minimum of 78 +/- 3% in 0 mM K+ to 155 +/- 15% in 15 mM K+. Vascular diameter increases were sustained for the full 5-minute test period only in 15 mM K+. In the epithelial portions of the cheek pouch, only the constrictor component of the potassium response was observed. The data indicate that potassium is sufficiently potent to participate in initiating functional hyperemia in striated muscle and might cause as much as a 6.3-fold increase in flow. Functional hyperemias exceeding approximately 3 minutes cannot be due to potassium ion, since the dilation induced by this agent is transient.
Selective inhibition by des-1-Asp-8-lle-angiotensin ii of the steroidogenic response to restricted sodium intake in the rat.
Authors: Sarstedt C A , Vaughan E D , Peach M J
Published: June 2012

Angiotensin III (des-1-Asp-angiotensin II) is a potent steriodogenic agent in many species. The effects of the heptapeptide in the adrenal zona glomerulosa are resistant to blockade by C-terminally substituted analogues of angiotensin II (1-Sar-8-Ile- or 1-Sar-8-Ala-octapeptides). For this reason, the effects of 7-Ile-angiotensin III, a C-terminally substituted analogue of the heptapeptide, and 1-Sar-8-Ile-angiotensin II on aldosterone biosynthesis in rabbit adrenal cortical cell suspensions and on urinary aldosterone excretion in sodium-deprived rats were studied. In the vitro studies, 7-Ile-angiotensin III was a better antagonist of angiotensin II- or angiotensin III-induced steroidogenesis than was 1-Sar-8-Ile-angiotensin II. In the rats, subcutaneously administered 1-Sar-8-Ile-angiotensin II (0.9 mumoles/kg) produced prolonged blockade of the pressor responses to exogenous angiotensin II. 70Ile-angiotensin III (0.9 mumoles/kg) had no effect on resting blood pressure or on blood pressure responses to angiotensin II infusions. At the doses studied, however, 7-Ile-angiotensin III caused a marked decrease (50%) in aldosterone excretion in sodium-deprived rats, but 1-Sar-8-Ile-angiotensin II had no effect on aldosterone excretion. In the sodium-deprived rats, the administration of 7-Ile-angiotensin Ile was not associated with an acute increase in plasma renin activity, but treatment with 1-Sar-8-Ile-angiotensin II resulted in a sixfold increase in plasma renin activity, but otensin III was not associated with an acute increase in plasma renin activity, but treatment with 1-Sar-8-Ile-angiotensin II resulted in a sixfold increase in plasma renin activity. These results are consistent with a role for angiotensin III in the control of aldosterone biosynthesis.