bluuebunny/crossref_metadata_2025 huggingface dataset:
Regional and Systemic Hemodynamic Patterns in Rabbits with Neurogenic Hypertension
Authors: ALEXANDER NATALIE , DeQUATTRO VINCENT
Published: June 2012

The hemodynamic basis of neurogenic hypertension was studied in unanesthetized rabbits 10 minutes to 30 days after sinoaortic denervation (SAD). The fractional distribution of
86
Rb to body tissues was determined and used to calculate regional blood flow from the value of cardiac output obtained from an arterial dilution curve of the indicator. Sham-operated rabbits served as controls. Increased cardiac output was a major hemodynamic component of SAD hypertension in 69% of the rabbits studied 1-40 hours postoperatively (acutely) but in only 25% of those studied 3-30 days after surgery (chronically). In the majority of the chronic SAD rabbits, increased total peripheral resistance (TPR) was the basis of the hypertension. All SAD rabbits had increased heart rates. Acutely, most high-cardiac output hypertensive rabbits had increased splanchnic resistance with normal blood flow, whereas all of them had low or normal renal resistance with high blood flow. Flows were increased in other major regions. Acutely, in the few high-TPR hypertensive rabbits, resistance was significantly increased in splanchnic tissue, liver, and carcass but not in the kidneys. Chronically, renal resistance was elevated in both types of hypertension. Chronic high-TPR rabbits had increased resistance in all major regions, but, unlike the acute high-TPR group, increased carcass resistance was located in bone rather than skeletal muscle. In the few chronic high-cardiac output hypertensive rabbits, TPR was reduced and regional blood flows were high with the exception of that to the kidneys and liver. Skin received a larger percent of cardiac output in chronic hypertensive rabbits than it did in acute hypertensive rabbits regardless of the hemodynamic basis of the hypertension.
Cholesteryl Ester Synthesis in Normal and Atherosclerotic Aortas of Rabbits and Rhesus Monkeys
Authors: Brecher Peter I. , Chobanian Aram V.
Published: June 2012

The formation of cholesteryl ester in aortic tissue was studied using subcellular fractions from normal and atherosclerotic rabbit and rhesus monkey aortas. The properties of two enzyme systems capable of esterifying 1-
14
C-oleic acid into cholesteryl ester in vitro were investigated, and increased activity was demonstrated for both systems as a result of cholesterol feeding. Microsomal preparations were used to study the ATP, CoA-dependent esterification which involves two enzymes, fatty acyl CoA synthetase and fatty acyl CoA: cholesterol acyltransferase. The properties of both enzymes were investigated, and an increase of about fourfold in activity of the acryltransfrease was demonstrated in aortic microsomes as a result of cholesterol feeding for 3-6 months. Esterification of oleic acid into cholesteryl ester by aortic high-speed supernatant fractions at an acidic pH was also observed; the enzyme system involved did not require cofactors, and its activity greatly increased as a result of cholesterol feeding. Similar increases in the activity of both esterifying enzyme systems were found when normal and atherosclerotic rhesus monkey aortic fractions were compared.
p
-Chlorophenoxyisobutyrate (CPIB) and 2-methyl-2-[
p
-(1, 2, 3, 4-tetrahydro-l-naphthyl)-phenoxy]propionic acid (TPIA) produced inhibition of both cholesterol-esterifying enzyme systems. TPIA was a more effective inhibitor than CPIB on both enzyme systems by at least an order of magnitude. These studies suggest that increased intracellular synthesis of cholesteryl ester by aortic tissue may contribute to its accumulation in atherosclerosis.
Activation Studies following Experimental Hemiblock in the Dog
Authors: Gallagher John J. , Ticzon Andres R. , Wallace Andrew G. , Kasell Jackie
Published: June 2012

Electrocardiograms (ECG), McFee vectorcardiograms (VCG), and ventricular activation data were collected from 25 anesthetized dogs before, immediately after, and 4 weeks after surgically induced discrete left anterior divisional block. Left anterior divisional block resulted in minor ECG changes: small S waves developed in leads II, III, and aVF and the QRS complex was prolonged 5-15 msec (mean 9 ± 2.7 [SD] msec). Prominent VCG changes also occurred: maximal and terminal forces were shifted posteriorly, superiorly, and slightly leftward, the duration of the loop was increased 5-15 msec (mean 9.8 ± 2.8 msec), and the terminal portions of the loop were slurred. Epicardial surface mapping revealed a consistent area of 5-20-msec delay (mean 12 ± 5.1 msec) confined to the lateral-basal surface of the left ventricle. Transmural activation studies in this area invariably revealed 6-20-msec (mean 12.8 ± 4.8 msec) delays in Purkinje and 3-25-msec (mean 12.4 ±5.6 msec) delays in endocardial activation. The wave front propagated across the wall with normal velocity. Q waves developed due to a "window effect" in the area of delay. Combining division of the septal fibers with left anterior divisional block resulted in surface delays of greater magnitude with marked axis shifts toward the left. Despite the extensive interconnections of the left ventricular conduction system, discrete proximal left anterior divisional block resulted in a significant alteration in the sequence of ventricular activation, confirming the fascicular nature of the left ventricular conduction system. The septal division appears to be an integral part of this system. The methodology described in this paper can be used to readily differentiate between epicardial delay due to conduction delay and that due to intramural myocardíal delay.
Cardiac Hypertrophy in Spontaneously Hypertensive Rats
Authors: Sen Subha , Tarazi Robert C. , Khairallah Philip A. , Bumpus F. Merlin
Published: June 2012

Ventricular weight in spontaneously hypertensive rats (F26 generation, Okamoto-Aoki strain) was significantly higher (
P
< 0.001) than that in body weight-matched American Wistar and Kyoto-Wistar normotensive rats, not only among older groups of rats but also among younger groups that had not developed significant hypertension. Deoxyribonucleic acid (DNA) concentration in ventricular muscle was not different from normal in the youngest group (
P
< 0.4) but was significantly reduced in the older spontaneously hypertensive rats (
P
< 0.01). Plasma renin activity was significantly increased in younger spontaneously hypertensive rats before the development of established hypertension; moreover, ventricular weight and plasma renin activity were significantly correlated in younger rats (
r
= 0.788,
P
< 0.005 for all rats,
r
= 0.644,
P
< 0.01 for spontaneously hypertensive rats). Antihypertensive therapy with either α-methyldopa or hydralazine reduced blood pressure, especially in hypertensive rats; however, ventricular weight was reduced by methyldopa (
P
< 0.01) but not by hydralazine. Plasma renin activity was reduced by methyldopa but increased by hydralazine (
P
< 0.01). DNA concentration was reversed toward normal by methyldopa but not by hydralazine. Similar results were obtained when methyldopa and hydralazine were given to younger rats to prevent hypertension. The changes in ventricular weight with the onset of hypertension and with its reversal or its prevention suggest that blood pressure might not be the sole factor contributing to cardiac hypertrophy in the spontaneously hypertensive rat and that the renin-angiotensin system might play a permissive role enhancing myocardial hypertrophy.
Left Ventricular Stiffness Associated with Chronic Pressure and Volume Overloads in Man
Authors: Grossman William , McLaurin Lambert P. , Stefadouros Miltiadis A.
Published: June 2012

The relative effects of chronic pressure overload and chronic volume overload on left ventricular diastolic chamber stiffness were examined using a combined hemodynamic and ultrasonic technique in 27 patients. The slope of the left ventricular pressure-diameter relation in late diastole was measured and found to be steep in the groups with pressure or volume overload (9.0 ± 1.8 mm Hg/mm for pressure overload, 5.6 ± 0.9 mm Hg/mm for volume overload) compared with a control group (2.2 ± 0.2 mm Hg/mm). When this slope was normalized for either pressure or diameter, chamber stiffness remained high in the pressure-overloaded ventricles but was only slightly increased in the volume-overloaded ventricles compared with control. Ventricular wall thickness was much greater in pressure-overloaded ventricles (15.6 ± 1.0 mm) than it was in normal (9.0 ± 0.4 mm) ventricles but only slightly increased in volume-overloaded ventricles (10.6 ± 0.9 mm). The large increases in both effective and normalized diastolic stiffness indexes associated with chronic pressure overload suggest an increase in intrinsic left ventricular chamber stiffness, possibly related to an increase in wall thickness. In contrast, chronic volume overload results in only slight increases in normalized diastolic stiffness indexes and wall thickness. It is suggested that differences in the pattern of hypertrophy, which result in a significant disparity in ventricular wall thickness between the two conditions, best account for the observed differences in diastolic left ventricular chamber stiffness.
Enhanced renal prostaglandin production in the dog. I. Effects on renal function.
Authors: Tannenbaum J , Splawinski J A , Oates J A , Nies A S
Published: June 2012

The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 and F2alpha.PGE2given at 0.01-0.3 mug/kg min--1 produced dose-related increases in urine flow, sodium and potassium excretion, free water clearance, and renal blood flow. The glomerular filtration rage increased only at the lowest dose and the calculated filtration fraction fell. Arachidonic acid at 1.0-30.0 mug/kg min--1 similarly produced dose-related increases in electrolyte excretion, but the increase in renal blood flow was much less than that produced by PGE2 and there were no changes in glomerular filtration rate, filtration fraction, or free water clearances. PGF2alpha had essentially no effects at infusion rates of 0.03-1.0 mug/kg min--1. All renal effects of arachidonic acid were inhibited by simultaneous infusions of an inhibitor of prostaglandin synthetase, 5, 8, 11,14-eicosatetraynoic acid (20:4). None of the effects produced by PGE2 were inhibited by 20:4. These results indicate that enhanced endogenous renal prostaglandin synthesis, which can be produced by arachidonate infusion, results in significant alterations of renal function. This finding strengthens the hypothesis that renal prostaglandins formed in vivo have physiological importance as regulators of renal function.
Pulmonary parenchymal tissue volume measurements in graded degrees of pulmonary edema in dogs.
Authors: Glauser F L , Wilson A F , Carothers L , Higi J , White D , Davis J
Published: June 2012

We investigated the accuracy and the sensitivity of a modification of the acetylene inhalation technique for the determination of lung tissue volume (Vt) during various grades of hemodynamic pulmonary edema in 23 dogs. After base-line acetylene measurements were obtained, intravascular driving force (pulmonary wedge pressure minus intravascular colloid osmotic pressure) was varied between -8 and +71 mm Hg by the inflation of an intra-aortic ballon and the infusion of isotonic saline. After 30 minutes at this new driving force, four timed acetylene samples were again collected. Vt (when factored by alveolar volume, VA) increased from base line to 0.23 plus or minus 0.07 ml/ml between a driving force of 0 and + 17 mm Hg. This same change in Vt/VA was accompanied by an increase in the lung wet weight-dry weight ratio from 3.84 plus or minus 0.31 to 5.2 plus or minus 0.25. Vt was 271 plus or minus ml compared with an actual lung wet weight of 288 plus or minus 57 g; Vt tended to overestimate lung wet weight in severe pulmonary edema. Alloxan-induced pulmonary edema (6 dogs) tended to parallel these data. We conclude that the acetylene method may ve a relatively accurate noninvasive method for the determination of increasing lung water in pulmonary edema.
Papillary muscle shortening in the intact dog; a cinderadiographic study of tranquilized dogs in the upright position.
Authors: Grimm A F , Lendrum B L , Lin H L
Published: June 2012

Shortening of the anterior papillary muscle of the left ventricle was demonstrated in six intact, tranquilized dogs. Two small metal markers that had been surgically implanted 3-50 months earlier were cineradiographically photographed during approximately ten sequential cardiac cycles in each of two orthogonal positions. Distances between markers were plotted for successive frames. The resulting curves were used to obtain maximum velocities of papillary muscle shortening and lengthening: 1.08 plus or minus 0.29 muscle lengths/sec and 1.39 plus or minus 0.48 muscle lengths/sec, respectively. From the two orthogonal planes, the average maximum spatial distance and the average minimum spatial distance between the markers were calculated. The mean percent shortening of 22.8 plus or minus 6.5% was surprisingly large: it approximated the distance from the foot to the peak of the ascending limb of the myocardial length-tension curve derived from isolated muscle studies. Mechanical studies on isolated papillary muscle have consistently shown reduced shortening with increasing loads. Since the in vivo dog papillary muscle has been reported to be under considerable tension during systole, there appears to be some contradiction between the degree of shortening found in the present study and the shortening observed in isolated papillary muscle studies.
Demonstration that the atria, ventricles, and lungs each are responsible for a tonic inhibition of the vasomotorcenter in the dog.
Authors: Mancia G , Donald D E
Published: June 2012

To localize the areas of the cardiopulmonary region involved in tonic inhibition of the vasomotor center, anesthetized dogs were subjected to sinoaortic denervation and diaphragmatic vagotomy. Afferent vagal nerve traffic was interrupted in the neck by cooling. With the venous return taken from the venae cavae, oxygenated extracorporeally, and returned to the aorta, the heart was removed, leaving the ventilated lungs (condition 1), and the lungs and the ventricles were removed, leaving the beating atria (condition 3). With the venous return taken from the pulmonary arteries, oxygenated extracorporeally, and returned to the left atrium, the lungs were removed, leaving the intact working heart (condition 2), and the lungs were removed and the atria were denervated, leaving the working innervated ventricles (condition 4). Vagal cooling increased aortic pressure by 25 plus or minus 2 (SE) mm Hg in condition 1, by 36 plus or minus 2 mm Hg in condition 2, by 29 plus or minus 2 mm Hg in condition 3, and by 29 plus or minus 7 mm Hg in condition 4. Removing the atria in condition 3 or denervating the ventricles in condition 4 abolished the reflex response. Thus, afferent vagal nerves from the lungs and the heart tonically inhibit the vasomotor center. The inhibition exerted by the heart is caused by receptors in the atria and the ventricles.
Red cell carriage of label: its limiting effect on the exchange of materials in the liver.
Authors: Goresky C A , Bach G G , Nadeau B E
Published: June 2012

The red cell membrane is a permeability barrier that limits the equilibration of a variety of solutes between red cell and plasma water. We utilized the multiple indicator dilution technique to investigate the effect of this barrier on the exchange in the liver of a group of tracer substances that are not removed in net fashion from the hepatic circulation: thiourea, urea, and chloride. We demonstrated that, after preequilibration of the label with red cells, a red cell carriage effect appeared (the trapping and translocation of label in the red cells), that this effect was most marked when the permeability of the red cell was relatively low for the substance under consideration (thiourea), and that the effect became small when the permeability of the red cells was large for the exchanging substance (urea and chloride). We developed a theoretical description of the retarding effect of the red cell permeability barrier on the extravascular exchange of label and were able to use this description to obtain estimates of the red cell permeability from the in vivo dilution curves. We examined the effect of plasma injection, of changing the input in such a fashion that the label was not preequilibrated with red cells, and found both experimentally and theoretically, that for substances of low permeability the transit time from these experiments, if multiplied by the total water flow or solute flux, gave an overestimate of both the apparent total volume of distribution and the mass of traced material in the system. This last effect is of great importance for the practical design of many biological experiments. Reliable volume and mass estimates can be made only when the labeled material has been preequilibrated with red cells.
Dynamics of glomerular ultrafiltration in the rat. VIII. Effects of hematocrit.
Authors: Myers B D , Deen W M , Robertson C R , Brenner B M
Published: June 2012

This study was undertaken in an effort to examine the effects of selective variations in systemic hematocrit on the preglomerular, glomerular, and postglomerular micocirculation in the rat. By isovolemic exchange transfusions, systemic hematocrit (control 51 ml/100 ml) was either reduced (21 ml/100 ml, N equal 7 rats) or elevated (62 ml/100 ml, N equal 7). Single nephron glomerular filtration rate varied inversely and filtration fraction varied directly with the changes in hematocrit. The fall in filtration fraction with decreased hematocrit was due to a decline in the measured glomerular transcapillary hydraulic pressure difference and to a marked increased in the initial glomerular plasma flow rate. Afferent (RA)and efferent (RE) arteriolar resistance declined with the fall in hematocrit; RA fell proportionately more than did RE. The rise in filtration fraction with the elevation in hematocrit was due to a marked increase in in part due to a relatively greater rise in RE than in RA. These findings provide an attractive explanation for the general tendency for filtration fraction to vary directly with hematocrit in anemic and polycythemic states in man.
Arterial lysosomes and connective tissue in primate atherosclerosis and hypertension.
Authors: Wolinsky H , Goldfischer S , Daly M M , Kasak L E , Coltoff-Schiller B
Published: June 2012

The cellular events that occur in the vessel wall consequent to changes in endothelial permeability result in the progression of vascular disease, particularly atherosclerosis. Female rhesus monkeys were fed an atherogenic diet or were made hypertensive for 6-8 months; and their vessels were then compared with vessels from control monkeys. Length-defined segments of coronary vessels, the thoracic aorta, and the abdominal aorta showed significant increases in total connective tissue in the atherosclerotic and hypertensive groups; pulmonary vessels did not. The diseased aortic segments had increased levels of two lysosomal enzymes, acid phosphatase and beta-N-acetylglucosaminidase; pulmonary vessels were not diseased and did not show these changes. Coronary vessels from the atherosclerotic and hypertensive groups did not show an increase in enzyme levels on biochemical measurements, but focal accumulations of lysosomes were identified by cytochemical techniques. In atherosclerotic lesions, a doubling of cholesterol and more than a tenfold increase in cholesterol ester were found. These connective tissue and lysosomal changes are early features of primate vascular disease and may result from the accumulation of excessive substrate (cholesterol ester) in the lysosomes of vascular smooth muscle cells.
Inherited depression of arterial lipoamide dehydrogenase activity associated with susceptibility to atherosclerosis in pigeons.
Authors: Zemplenyi T , Blankenhorn D H , Rosenstein A J
Published: June 2012

The activity of lipoamide dehydorgenase (E.C.1.6.4.3) was measured in arterial homogenates from very young pigeons (5-8 weeks old) known to differ in their susceptibility to atherosclerosis. The activity of the arterial enzyme was significantly lower in the atherosclerosis-susceptible White Carneau pigeons than it was in the atherosclerosis-resistant Show Racer pigeons. Lipoamide dehydrogenase is a component of the pyruvate dehydrogenase and alpha-ketoglutarate multienzyme complexes. The first complex catalyzes the conversion of pyruvate to oxaloacetate via acetyl-CoA, and this reaction represents a crucial link between glycolysis and the Krebs cycle. The second complex is essential for the oxidative breakdown of carbohydrates, fats, and amino acids via the Krebs cycle. Reduced activity of these complexes, resulting from low activity of lipoamide dehydrogenase, favors reduction of pyruvate to lactate and a shift to glycolysis. This situation is in accord with other results obtained in avian and human arteries which appear to indicate a higher rate of glycolysis in atherosclerosis-susceptible and atherosclerotic arteries. It appears that the increased dependence of the White Carneau arteries on glycolysis, suggested by the reduced lipoamide dehydrogenase activity, facilitates the development of atherosclerosis in this pigeon strain.
Simulation of action potential propagation in an inhomogeneous sheet of coupled excitable cells.
Authors: Joyner R W , Ramón F , Morre J W
Published: June 2012

Cable theory and active equivalent circuits have been used to simulate the propagation of action potentials along a single nerve or muscle fiber by representing the cell as a unidimensional cable composed of isopotential segments. We extended this method to a two-dimensional sheet of cells which in many ways represents the atrium. Our method consisted of solving for the potential profile of a sheet composed of a large number of isopotential membrane patches, each of which was represented by an active equivalent circuit in which the ionic conductances were functions of voltage and time. The patches were arranged in a rectangular array with resistive interconnections that could be varied over the sheet. We used this model to study the effect of various inhomogeneities on conduction velocity and the resulting wave fronts in a sheet of excitable tissue. Some of these inhomogeneities included different effective internal resistances in the x and y directions, preferential pathways, and discrete regions of changing resistive connections. The results showed that very localized changes in membrane properties or cellular interconnections produce changes in the wave front over broad areas. This model provides a method for computing the wave fronts of action potential propagation in any two-dimensional inhomogeneous sheet of coupled excitable cells.
Regulation of glomerular filtration and proximal tubule reabsorption.
Authors: Knox F G , Cuche J-L  , Ott C E , Diaz-Buxo J A , Marchand G
Published: June 2012

In this review current hypotheses for the regulation of filtration rate and the subsequent reabsorption of that filtrate by the proximal tubule are discussed. In the rat the filtration rate is highly plasma flow dependent because of the phenomenon of filtration equilibrium. On the other hand, in man and dog filtration rate is much less dependent on renal plasma flow. In these species glomerular capillary pressure rather than glomerular plasma flow may be the primary determinant of filtration. Three hypotheses for the autoregulation of glomerular filtration are discussed. Of these the myogenic theory, which holds that increases in perfusion pressure result in an intrinsic contraction of the smooth muscle in the walls of the afferent arterioles, remains the best, if not completely adequate, explanation for the phenomenon. The role of a macula densa feedback mechanism is controversial, although data are presented which strongly militate against this hypothesis. Similarly, the prostaglandins, although important in determining vascular resistance, probably do not mediate autoregulation. Two prevalent hypotheses for the regulation of fluid reabsorption by the proximal tubule, the physical factor hypothesis and the humoral hypothesis, are discussed. Data presented indicate that peritubule Starling forces have a marked effect on isotonic reabsorption by the proximal tubule in the presence of volume expansion and enhanced backleak into the proximal tubule lumen. However, in hydropenia and diminished backleak, changes in peritubule capillary Starling forces have little effect on proximal sodium reabsorption. Thus, the physical factor mechanism is a rather insensitive regulator of proximal reabsorption in the absence of volume expansion. Hormones known to regulate sodium transport per se, such as aldosterone, have no effect on sodium reabsorption by the proximal tubule. In contrast, those hormones primarily regulating anion reabsorption in the proximal tubule, such as parathyroid hormone, have significant effects on fluid reabsorption. Thus, the humoral regulation of anion reabsorption has secondary effects on proximal sodium reabsorption.
Identification of angiotensinogenic hypertension in man using 1-sar-8-ala-angiotensin II (Saralasin, P-113).
Authors: Streeten D H , Freiberg J M , Anderson G H , Dalakos T G
Published: June 2012

Peripheral plasma renin activity (PRA) is not invariably elevated in patients whose ischemic renal lesion is causing hypertension. Infusions of an angiotensin II antagonist, 1-sar-8-ala-angiotensin II (P-113), have been used to determine whether the blood pressure responses might indicate angiotensin dependence in 221 consecutive hypertensive patients. In 32 patients P-113 infusion reversibly reduced blood pressure, and almost all of these "P-113 responders" had elevated renal vein and/or peripheral PRA levels, together with evidence of renal ischemia. Among the 189 "P-113 nonresponders," peripheral PRA was elevated in seven (3.8%), and renal vein PRA ratio was abnormal in two patients, who might represent exceptions to the otherwise successful record of the P-113 response in identifying "angiotensinoginic" hypertensives.
Changes in renin, water balance, and sodium balance during development of high blood pressure in genetically hypertensive rats.
Authors: Bianchi G , Baer P G , Fox U , Duzzi L , Pagetti D , Giovannetti A M
Published: June 2012

In genetically hypertensive rats of the Milan hypertensive strain (MHS) and normotensive rats (NR) developed from the same Wistar stock colony, blood pressure (BP), plasma renin activity (PRA), sodium balance, and water balance were measured from the time of weaning to the seventh week postweaning in three separate but essentially identical experiments. In a fourth experiment, total and extracellular water, total sodium, and exchangeable sodium were measured in MHS and NR at 24 and 130 days of age. Although the time course of changes varied slightly between experiments, BP of both NR and MHS rose until the second and third weeks postweaning, at which time BP in MHS was 40 to 50 mm Hg higher than in NR. PRA in MHS was one-half that of NR at weaning. Increasing BP was accompanied by falling PRA in both, and PRA was not significantly different when stable, adult blood pressure was reached. Urinary volume in MHS was 50% to 100% greater (P less than 0.001) than in NR at weaning and for a few days after. Sodium was retained to a greater extent by MHS during the period when the blood pressure difference develops, from weaning to the fourth week postweaning. This sodium retention (MHS = 97.0 plus or minus 10.3, NR = 65.2 plus or minus 6.8 SE mu-Eq Na retained/g body weight gain; P less than 0.005) is the result of significantly lower urinary excretion of dietary sodium by MHS. A causative role for the kidney is suggested in the established of high blood pressure in MHS.
Plasma renin and sodium balance during development of moderate and severe renal hypertension in rats.
Authors: Leenen F H , de Jong W
Published: June 2012

The changes in systolic blood pressure, plasma renin activity (PRA), and sodium balance were studied during the first 3 weeks of the development of renal hypertension in rats with an undisturbed contralateral kidney. Moderate hypertension (160 to 180 mm Hg) was reached after application of a 0.25-mm solid clip; severe hypertension (200 to 230 mm Hg) developed after application of a 0.20-mm solid clip. Basal levels of PRA in peripheral blood increased only in rats with a 0.20-mm clip, when blood pressure had already risen to 160 to 180 mm Hg. Elevated peripheral PRA, however, may have contributed to the initial increase of blood pressure in both groups of hypertensive rats, as indicated by higher late-afternoon PRA values at the peak of the normal diurnal rhythm of PRA. PRA in renal venous blood from the clipped kidney increased during the development of both moderate and severe hypertension at a rate quantitatively related to the rise in blood pressure. During the first 8 to 10 days after application of both sizes of clips, sodium retention per gram gain in body weight was significantly higher than in the sham-operated controls. Subsequently, sodium balance and blood pressure stabilized in animals with a 0.25-mm clip. In the rats with a 0.20-mm clip, sodium balance returned to control levels and became even lower than in the sham-operated group. Despite this negative sodium balance, blood pressure showed a further rise. These results suggest that in rats with an undisturbed contralateral kidney, a positive sodium balance has a role in the early phase of the development of renal hypertension. The enhanced plasma renin activity also probably contributes to the early phase, but appears to make a major contribution to the further development of severe hypertension.
Effect of prolonged low-dose angiotensin II infusion on the sensitivity of adrenal cortex in man.
Authors: Oelkers W , Schöneshöfer M , Schultze G , Brown J J , Fraser R , Morton J J , Lever A F , Robertson J I
Published: June 2012

The effect of incremental infusions of isoleucine-5-angiotensin II on blood pressure and plasma aldosterone concentrations was studied in normal man before and after 66 hours of intravenous infusion of angiotensin II at 2 ng kg-1 min-1, sodium and potassium balance being kept roughly constant throughout. Plasma sodium and ACTH concentrations were unaltered, but plasma potassium and magnesium levels and basal plasma cortisol fell slightly after prolonged angiotensin administration. During the prolonged angiotensin infusion plasma renin activity was suppressed, and there was a sustained elevation of arterial pressure and plasma aldosterone concentration. Aldosterone excretion, while clearly increased, showed a regular circadian rhythm, with peak values in the early morning. The angiotensin II-pressor relationship was not significantly changed after the prolonged infusion of angiotensin II, while the angiotensin II-aldosterone dose-response curve was steeper than in the basal state but not identical with that of sodium depletion. No differences were observed in the pressor or aldosterone-stimulant effects of the isoleucine-5 and valine-5 forms of angiotensin II. A trophic effect of angiotensin II on the adrenal cortex may provide a partial explanation for the enhanced response of aldosterone to angiotensin II in sodium depleted man.
Role of angiotensin II and potassium in the long-term regulation of aldosterone secretion in intact conscious dogs.
Authors: McCaa R E , McCaa C S , Guyton A C
Published: June 2012

The aldosterone response to long-term infusion of angiotensin II and potassium was studied in intact conscious dogs. Plasma aldosterone concentration (PAC), plasma renin activity (PRA), and plasma cortisol concentration (PCC) were determined by radioimmunoassay. In ten dogs maintained on angiotension II infusion (5 ng/kg min-1) for 14 days, PAC increased from 6.9 plus or minus 2.9 to 18.6 plus or minus 4.7 ng/100 ml plasma (mean plus or minus SE) within ten minutes after beginning the infusion, reached a maximum level of 28.3 plus or minus 6.8 ng/100 ml plasma by one hour, and returned to control levels by six hours. PCC increased from 0.6 plus or minus 0.2 to 3.9 plus or minus 1.0 mu-g/ 100 ml plasma within one hour after angiotensin II infusion and returned to control levels by six hours. During the next 14 days of angiotensin infusion, PAC remained at control levels, PRA was undetectable by radioimmunoassay, and mean arterial blood pressure was elevated 29 plus or minus 4 mm Hg above control levels. In ten dogs maintained on KCL infusion (250 mEg/day) for 15 days, PAC increased from 6.8 plus or minus 2.4 to 13.6 plus or minus 3.4 ng/100 ml plasma within 24 hours, averaged 22.4 plus or minus 4.3 ng/100 ml plasma by 48 hours, and remained elevated for the next 12 days, averaging 21.8 plus or minus 5.6 ng/100 ml plasma. During the next 14 days of KCL infusion, serum Kn increased from 4.1 plus or minus 0.3 to 4.9 plus or minus 0.5 ME1/L, and PRA decreased from 1.25 plus or minus 0.3 to 0.65 plus or minus 0.2 ng/ml/hr. PCC averaged 0.73 plus or minus 0.4 mu-g/100 ml plasma in the control samples and failed to change significantly during KCL infusion. These data indicate that chronic angiotensin II infusion into intact conscious dogs at rates capable of maintaining elevated arterial blood pressure results in a transient increase in aldosterone secretion that lasts only a few hours, while chronic infusion of potassium ions at rates that produce a minor increase in serum Kn results in a sustained increase in aldosterone secretion.
Changes in myocardial blood flow and S-T segment elevation following coronary artery occlusion in dogs.
Authors: Smith H J , Singh B N , Norris R M , John M B , Hurley P J
Published: June 2012

The relationship between regional blood flow and epicardial S-T segment elevation was studied in 26 open-chest anesthetized dogs with left anterior coronary artery ligations. Changes in myocardial blood flow, measured with 15 plus or minus 5mu (diameter) microspheres labeled with 141-Ce, 85-Sr, and 169-Yb, were correlated with summated S-T segment elevations 15 minutes, 1 hour, and 2 hours after coronary artery occlusion. In normal areas, myocardial blood flow was 113 plus or minus 5 ml/min 100 g- minus 1 and summated S-T segment elevation was 0.3 plus or minus 0.2 mv. Fifteen minutes after coronary artery occlusion in 26 dogs, S-T segment elevation was 5.7 plus or minus 0.7 mv over the center of the infarct and myocardial blood flow was 10 plus or minus 1 ml/min 100 g- minus 1; over the border zone, myocardial blood flow was 63 plus or minus 4 ml/min 100 g- minus 1 and S-T segment elevation was 3.1 plus or minus 0.1 mv. One third of the areas with a myocardial blood flow of 10 ml/min 100 g- minus 1 or less had no S-T segment elevation. In the center and border zones of the infarct in 9 dogs, myocardial blood flow increased from 11 plus or minus 2 and 67 plus or minus 8 ml/min 100 g- minus 1 15 minutes after occlusion to 20 plus or minus 4 and 84 plus or minus 12 ml/min 100 g- minus 1, respectively, 2 hours after coronary artery occlusion. These increases were not associated with a significant reduction in summated S-T segment elevation. The results do not suggest a simple quantitative relationship between epicardial S-T segment elevation and myocardial blood flow following acute coronary artery occlusion.
Prostaglandin synthesis by bovine mesenteric arteries and veins.
Authors: Terragno D A , Crowshaw K , Terragno N A , McGiff J C
Published: June 2012

Prostaglandins (PG) were synthesized at similar rates by bovine mesenteric arteries and veins; viz., ca. 200 ng/g wet weight after one hour of incubation. After synthesis, PGE and PGF compounds were released from slices of arteries and veins into the incubating medium; PG were not detected in the walls of these blood vessels. Arachidonic acid, the precursor to PGE-2 and PGF-2-alpha, did not affect PG synthesis, whereas meclofenamate, an aspirin-like agent, decreased synthesis in arteries and veins by 90%. The PG biosynthetic capacity of these blood vessels is high, as indicated by greater than 20% conversion of (1-14C)-arachidonic acid to radiolabeled PG. Under control conditions in both arteries and veins, synthesis of PGE-2 exceeded that of PGF-2-alpha twofold. Bradykinin selectively increased the synthesis of a PGE-like substance in arteries and of a PGE-like substance in veins.
Influence of the renin-angiotensin system on the effect of prostaglandin synthesis inhibitors in the renal vasculature.
Authors: Satoh S , Zimmerman B G
Published: June 2012

The effect of meclofenamate and indomethacin on renal blood flow and renal vascular resistance was determined under basal experimental conditions and during renal ischemia in pentobarbital-anesthetized dogs. Renal blood flow was measured with an electromagnetic flowmeter and renal arterial pressure was recorded from a catheter in the renal artery. Intra-arterial infusion of indomethacin or meclofenamate in concentrations of 4 and 4 to 8 mu-g/ml, respectively, did not cause any significant change in renal blood flow or renal vascular resistance under basal conditions. During the period of ischemia (50% reduction in renal blood flow), 4 mu-g/ml of either prostaglandin synthetase inhibitor caused a marked increase in renal vascular resistance. Prostaglandin E in the renal venous blood was decreased at the time renal vascular resistance was increased by meclofenamate. The renal vasoconstrictor response to angiotensin II injected intravenously was potentiated by both inhibitors under basal as well as ischemic conditions, which also suggested that prostaglandin synthesis was inhibited. The angiotensin antagonist 1-sar-8-ala-angiotensin II was infused intra-arterially in concentrations of 20 and 40 mmu-g/ml during renal ischemia. Subsequent administration of meclofenamate increased renal vascular resistance only slightly. The results of these experiments indicated that renal prostaglandins have more influence on renal blood flow during renal ischemia than under basal conditions, and that the renin-angiotensin system may be involved in activating synthesis and release of prostaglandins during ischemia.
Disappearance of bradykinin in the renal circulation of dogs. Effects of kininase inhibition.
Authors: Nasjletti A , Colina-Chourio J , McGiff J C
Published: June 2012

In chloralose-anesthetized dogs, we investigated the disappearance of bradykinin on passage across the renal circulation. The peptide was infused into a renal artery at various doses (5-200 ng/kg min-1); renal blood flow and the concentration of kinins in renal venous blood were then determined and the percent survival of bradykinin on passage through the kidney calculated. Bradykinin caused a dose-related increase in renal blood flow, urine flow, sodium excretion, and kinin content of renal venous blood. Intravenous administration of BPP9alpha (300 mug/kg), a peptide kininase II inhibitor, potentiated the renal vasodilator, diuretic, and natriuretic actions of bradykinin and augmented the survival of the kinin on passage through the kidney from 12.72 +/- 1.64% in control dogs to 53.92 +/- 7.48% (P less than 0.001). Furthermore, the values of peptide survival were positively correlated with the increases in renal blood flow (r = 0.92, P less than 0.01), urine flow (r = 0.75, P less than 0.01), and sodium excretion (r = 0.68, P less than 0.01) produced by bradykinin. In addition, BPP9alpha by itself increased renal blood flow (16%, P less than 0.01), urine flow (115%, P less than 0.005), and sodium excretion (167%, P less than 0.02). Similarly, the concentration of kinin in renal venous blood and the excretion of urinary kinins rose from 0.11 +/- 0.03 ng/ml and 4.1 +/- 1.1 ng/min to 0.24 +/- 0.05 ng/ml (P less than 0.005) and 38.5 +/- 12.2 ng/min (P less than 0.02). These studies suggest that kinins generated intrarenally play a role in the regulation of renal blood flow and salt-water excretion and that variations in the capacity of the kidney to inactivate kinins may be a determinant of the intrarenal activity of the kallikrein-kinin system.
Vascular angiotensin II receptors and sodium balance in rats. Role of kidneys and vascular renin activity.
Authors: Swales J D , Tange J D , Thurston H
Published: June 2012

The relationship between the vascular response. to angiotensin II and sodium balance was studied by measuring the volume of specific antiserum needed to block the pressor response to a standard dose of angiotensin II in rats. In normal rats, sodium depletion reduced the volume of antiserum required to prevent a pressor response to 50 ng of angiotensin II from 0.32 to 0.22 ml; sodium loading increased the volume required to 0.65 ml. After bilateral nephrectomy, there was a progressive increase in the antibody requirement to a maximum of 0.63 ml at 6 hours. At this stage, there was no change in the blocking requirement with sodium depletion by either pretreatment with a low-salt diet (0.60 ml) or peritoneal dialysis (0.62 ml). The pressor response to a 50-ng bolus of angiotensin II was closely correlated with the antibody requirement in all experiments (r equals plus 0.93). These observations indicate that sodium-induced changes in the vascular response to angiotensin II require the presence of kidney tissue. We suggest that such changes in response are mediated by alterations in vascular renin which generates angiotensin II at an arteriolar site that is not accessible to antibody molecules. This locally formed angiotensin II reduces the number of receptors free to respond to circulating angiotensin II and raises the threshold of the pressor response
Reflex parasympathetic coronary vasodilation elicited from cardiac receptors in the dog.
Authors: Feigl E O
Published: June 2012

Veratrum alkaloids injected into the coronary circulation stimulate myocardial receptors to produce reflex bradycardia and arterial hypotension (the Bezold-Jarisch reflex). This study investigated the hypothesis that parasympathetic coronary vasodilation occurs as part of the Bezold-Jarisch reflex. Blood flow in the circumflex coronary artery was measured in chloralose-anesthetized, closed-chest dogs with a newly developed cannula-tip flow transducer. Alpha-receptor blockade with Dibozane (2 mg/kg) was used to prevent peripheral vasodilation, and beta-receptor blockade with propranolol (1 mg/kg) was used to prevent adrenergic cardiac effects. Electrical pacing was used to maintain a constant heart rate. Under these conditions, veratridine injected into the anterior descending coronary artery but not into the circumflex coronary artery produced a 63% increase in circumflex coronary blood flow and an 88% increase in diastolic coronary conductance. The effect was abolished when the reflex arc was interrupted by either vagotomy or atropine administration. It is concluded that a cardiocoronary reflex parasympathetic coronary vasodilation can be elicited by stimulating cardiac receptors with veratridine.
Analysis of changes in reactivity of rabbit arteries and veins two weeks after induction of hypertension by coarctation of the abdominal aorta.
Authors: Bevan J A , Bevan R D , Chang P C , Pegram B L , Purdy R E , Su C
Published: June 2012

Vessel dimensions and characteristic responses to norepinephrine were measured in various arteries and veins of the rabbit made hypertensive by partial constriction of the upper abdominal aorta. The ear, radial, and basilar arteries taken from the circulation proximal to the ligature (the hypertensive arteries) were thickened in proportion to the rise is arterial blood pressure. The water, sodium, and potassium contents of these and all other vessels were not significantly changed in the hypertensive rabbits. The maximum response to norepinephrine in the ear artery, a representative vessel from the hypertensive part of the rabbit, was increased, whhereas the sensitivity of this vessel to norepinephrine expressed as the ED50 did not alter with changes in the arterial blood pressure. In contrast, the thickness and the maximum response to norepinephrine of the saphenous artery, representative of vessels distal to the ligature (normotensive vessels) and of the saphenous and cephalic veins were unaltered. The sensitivity as indicated by the norepinephrine ED50 of the veins, but not of the saphenous artery, increased with a rise in carotid artery blood pressure. These results suggest that the increased responsiveness to norepinephrine of arteries proximal to the ligature is due to changes in muscle mass and that the increased responsiveness of the veins is due to increased sensitivity to norepinephrine.
Visceromotor organization within descending spinal sympathetic pathways in the dog.
Authors: Barman S M , Wurster R D
Published: June 2012

The organization within the descending sympathetic pathways on the surface of the dorsolateral funiculus of the spinal cord was investigated in anesthetized dogs. Changes in heart rate and carotid, renal, and femoral resistances were calculated during electrical stimulation of the descending spinal sympathetic pathways; the location within the pathway of the maximum change in each of these parameters was then determined. Blood pressure increased at each stimulation point with the maximum increase at 3-3.5 mm ventrolateral to the dorsolateral sulcus (DLS). The maximum increases in carotid, renal, and femoral resistances occurred with stimulation at 0.5-1.5, 2, and 3 mm ventrolateral to the DLS, respectively. Maximum heart rate responses were elicited by stimulation 2 mm ventrolateral to the sulcus. These data demonstrate that the pathway is organized in a dorsal-to-ventral manner, with the most rostral parts of the body being represented most dorsally and the more caudal parts being represented more ventrally.
Effects of an inotropic agent, RO 2-2985 (X-537A), on regional blood flow and myocardial function in chronically instrumented conscious dogs and anesthetized dogs.
Authors: Hanley H G , Lewis R M , Hartley C J , Franklin D , Schwartz A
Published: June 2012

RO 2-2985 produced a marked positive inotropic effect in unanesthetized, chronically instrumented dogs, measured as an increase in left ventricular dP/ dt and an increase in maximum velocity of myocardial fiber shortening. Similar changes produced in dogs in hemorrhagic shock lasted for 2-3 hours. RO 2-2985 increased peripheral blood flow and caused marked increases in both coronary and renal blood flows. The drug altered the response of the renal vascular bed to subsequent norepinephrine administration. After administration of a single dose of RO 2-2985, norepinephrine produced sustained increases in renal blood flow, and this altered responsiveness to norepinephrine persisted for periods ranging from 1 to 3 weeks.