bluuebunny/crossref_metadata_2025 huggingface dataset:
Dissociation between renin and arterial pressure responses to beta-adrenergic blockade in human essential hypertension.
Authors: Bravo E L , Tarazi R C , Dustan H P , Lewis J W
Published: June 2012

Studies were carried out in 69 patients with essential hypertension to examine the relationship between changes in plasma renin activity (PRA) and arterial pressure (BP) in response to a beta-adrenergic blocking agent, propranolol. PRA had no consistent relationship with BP during treatment, either in patients receiving propranolol alone (r = 0.12) or in those receiving a combination of diuretics and propranolol (r = 0.18). Furthermore, long-term beta-adrenergic blockade failed to inhibit increases of PRA induced by diuretics or rapid sodium depletion. These results indicate that (1) beta-adrenergic blockade can reduce BP by mechanisms other than PRA suppression; and (2) the beta-adrenergic nervous system is important, but not essential, for renin release.
Dopamine induced relaxation of isolated canine renal, mesenteric, and femoral arteries contracted with prostaglandin F2-alpha.
Authors: Goldberg L I , Toda N
Published: June 2012

The purpose of this investigation was to develop a system for studying the effects of dopamine on isolated blood vessels. Canine renal, mesenteric, and small femoral arteries (less than 1 mm outside diameter) were exposed to phenoxybenzamine 10-5 M for one hour and contracted with prostaglandin F2-alpha. Cumulative concentrations of dopamine ranging from 10-6 to 10-4 M caused dose-related relaxation of the arteries. Propranolol 10-6 M did not affect the relaxation in concentrations which markedly antagonized the effects of isoproterenol. Large femoral arteries (greater than 1 mm outside diameter) did not relax with similar concentrations of dopamine. N-methyldopamine (epinine) produced similar relaxation; 3-methoxytyramine was inactive. Specific antagonism could not be demonstrated by the postulated dopamine antagonists-haloperidol, chlorpromazine, apomorphine, or bulbocapnine-in concentrations up to 10-5 M. Higher concentration of these agents could not be used because they caused the arteries to relax. This study demonstrated that PGF2-alpha-contracted arteries pretreated with phenoxybenzamine are suitable for further investigations of putative dopamine agonists and antagonists.
Effect of increased vascular pressure on lung fluid balance in unanesthetized sheep.
Authors: Erdmann A J , Vaughan T R , Brigham K L , Woolverton W C , Staub N C
Published: June 2012

In 20 unanesthetized sheep, we measured lung lymph flow and lymph and plasma protein concentrations during steady-state base-line conditions and during steady-state elevations of pulmonary microvascular hydrostatic pressure (range 3 to 23 cm H2O). In every sheep there was a base-line lung lymph flow (average 5.7 +/- 2.5 (SD) ml/hour), demonstrating that net fluid filtration occurred. The base-line lymph-plasma total protein ratio averaged 0.69 +/- 0.05, indicating a high protein osmotic pressure in the interstitial fluid at the filtration site. Lymph flow increased and lymph protein concentration decreased approximately linearly whenever hydrostatic pressure rose. A new steady-state condition was reached in 1-2 hours. The difference in plasma-to-lymph protein osmotic pressure increased by half the hydrostatic pressure increment (50% negative feedback regulation). Extravascular lung water content, measured post-mortem, did not change significantly until microvascular hydrostatic pressure more than doubled, indicating a large safety factor that protects the lungs against fluid accumulation normally. The major contributions to the safety factor appeared to be a sensitive and efficient lymph pump coupled to a washout of interstitial protein. The fluid filtration coefficient, whose calculation required many assumptions, averaged 1.64 +/- 2.65 ml/(cm H2O times hour) in the base-line condition and did not change significantly over the pressure range studied.
Glycoside inotropy in the absence of an increase in potassium efflux in the rabbit heart.
Authors: Poole-Wilson P A , Langer G A
Published: June 2012

The inotropic effect of 1.25 times 10(-6)M acetylstrophanthidin (ACS) and the influx and efflux of labeled potassium (42K+) were studied in the arterially perfused rabbit interventricular septum under control conditions and during respiratory acidosis. An increase in the CO2 content of the gas mixture with which the modified Ringer's solution was equilibrated from 5 to 30% reduced the perfusate pH from 7.37 to 6.66. The increment in developed tension in the presence of ACS was 3.0 +/- 0.2 g (n equals 10) under control conditions, but it was greater, 7.1 +/- 0.9 g (N equals 9) during acidosis (P less than less than 0.001). The net K+ loss due to an increase in K+ efflux was 1.8 +/- 0.2 mmoles/kg wet weight in control experiments but only 0.1 +/- 0.1 mmoles/kg net weight under acidotic conitions (P less than less than 0.001); in seven of nine experiments in respiratory acidosis, no increase in K+ efflux occurred despite a marked positive inotropy. In three septums, K+ influx was reduced by ACS during respiratory acidosis. These results demonstrate that during acidosis ACS inhibits sodium-potassium adenosinetriphosphatase (Na+-K+ ATPase) and causes an inotropic effect but does not increase K+ efflux. K+ efflux cannot be linked to calcium (Ca2+) influx or regarded as the controlling factor of glycoside-induced inotropy. The results give further support to the proposal that digitalis-induced inotropy is secondary to an enhancement of a Na+-Ca2+ exchange system.
Stress, deformation, and atelectasis of the lung.
Authors: Fung Y C
Published: June 2012

The lung parenchyma as a tissue has a rather unusual stress-strain relationship. A theoretical derivation of this relationship is presented which connects the surface tension and the tissue elastic stress in the alveolar septa with the alveolar geometry. The mathematical expression contains a few meaningful physical constants which can be determined by in vitro and in vivo experiments. With this stress-strain relationship, the general equations of lung mechanics are formulated, and solutions to some simpler problems are presented. First, the equilibrium of a lung subjected to a uniform inflation pressure (definition: alveolar air pressure - intrapleural pressure - pleural tension X mean curvature of pleura) is analyzed, and the stability of the equilibrium states with respect to small perturbations is examined. Second, an exact solution for a lung in a chest under the influence of gravity is presented; the solution is "exact," of course, for only a particular lung, but it can serve as a standard to check numerical procedures being developed in many laboratories. Finally, three types of possible atelectasis-planar, axial, and focal-are analyzed. The planar type can exist in a normally inflated lung, provided the layers of alveoli are forced to collapse toward a plane by some external agent. But axial atelectasis (alveoli collapse into a cylinder) can occur only if the dimension (at which the elastic tension in the alveolar septa vanishes). Similarly, focal atelectasis can occur only if the entire lung is smaller than the resting volume.
Interaction of sequential stimuli applied during the relative refractory period in relation to determination of fibrillation threshold in the canine ventricle.
Authors: Tamargo J , Moe B , Moe G K
Published: June 2012

An ineffective stimulus applied to cardiac tissue within the relative refractory period can alter the response to an immediately subsequent stimulus. We observed three response patterns that can coexist at different sites of stimulation in the same heart. In the first pattern, a stimulus of two to ten times diastolic threshold, applied too early to elicit a propagated response, becomes effective when a stimulus of equal strength is delivered 10 msec earlier. In the second pattern, a stimulus applied just late enough to evoke a response fails to do so when a stimulus of equal strenght precedes it by as much as 30 msec. Finally, in the third pattern, two stimuli, separated by 10 msec, both of which are late enough to be effective when they are given alone, fail to yield a propagated response when they are applied together. These results have a bearing on the use of trains of stimuli to assess the ventricular fibrillation threshold. Possible interpretations are based on the temporal dispersion of recovery from the refractory state.
Acetylcholine-induced reversal of canine and feline atrial myocardial depression during stretch, cardiac failure, and drug toxicity.
Authors: Gelband H , Myerburg R J , Hoffman B F , Bassett A L
Published: June 2012

Microelectrode and isometric recording techniques were used to evaluate the effects of acetycholine (ACh) on depressed isolated preparations of dog and cat atrial muscle. Atrial muscles were maintained at 36-37 degrees C with warmed Tyrode's solution and were stimulated at frequencies of 30 or 60/min. Depolarization to resting potentials of approximately -50 mv was noted (1) after excessive stretch was applied, (2) in muscles obtained from cats in overt right heart failure, and (3) during exposure of the muscles to excessive concentrations of acetylstrophanthidin or lidocaine. Depolarized muscles demonstrated action potentials of smaller amplitude and rate of rise. Exposure to ACh (2.7 X 10(-6)M) had a minimal effect on resting potential in normal dog and cat atrial muscle and was accompanied by significant negative inotropic actions. The same concentration of ACh markedly increased resting potential and action potential amplitude and induced positive inotropic effects in depolarized muscles; these effects also occurred during beta-adrenergic blockade. We suggest that the positive inotropic effect of ACh in depressed muscles may result from (1) a more synchronous contraction of cells within each muscle, (2) recruitment of previously quiescent cells in contraction, (3) possibly increased calcium inflow in individual cells during depolarizations of greater magnitude, and (4) an increase in the number of interacting sites between actin and myosin after resting potential is improved.
Calcium-accumulating properties of subcellular fractions of bovine vascular smooth muscle.
Authors: Ford G D , Hess M L
Published: June 2012

This study examined the calcium transport properties of two subcellular fractions of bovine aorta obtained by differential centrifugation. The vesicular fraction had a high-affinity (Km = 1.05 X 10(-6)M) calcium transport mechanism which could be potentiated by using the calcium-precipitating anion, oxalate. The mitochondria-enriched fraction's calcium transport system had a lower affinity for calcium than did that of the vesicular fraction. The calcium capacity of the vesicular fraction was determined by comparing the steady-state calcium uptake in the presence of oxalate in the whole homogenate with the same uptake by the vesicular fraction alone. A calcium capacity of about 100 mumoles Ca2+/kg aorta was obtained. It is concluded that the vesicular fraction has all of the properties of a major site of subcellular calcium regulation in vascular smooth muscle.
Active and passive immunization against angiotensin II in the rat and rabbit. Evidence for a normal regulation of the renin-angiotensin system.
Authors: Oster P , Bauknecht H , Hackenthal E
Published: June 2012

Active or passive immunization has been used repeatedly as a tool in studies on the role of the renin-angiotensin system in the control of blood pressure and kidney function. The results are not consistent among each other, and they are also at variance with other studies using different approaches. To evaluate the possible causes of these discrepancies, the biological characteristics of angiotensin antibodies were studied in rats. Following the intravenous injection of angiotensin II antibodies (purified by affinity chromatography), the plasma concentration of the antibodies declined in a two-exponential curve with half times of 11 hours and 7 days, which probably reflect distribution in the extracellular space and elimination, respectively. Plasma angiotensin II levels rose from preinjection levels of 100 pg/ml to 12,000 pg/ml within 10 minutes and then declined concomitantly with the decline in antibody concentration. We calculated that only a samll fraction of the circulating antibody was occupied by angiotensin II. Plasma renin concentrations were initially elevated both in controls and in antibody-injected rats, but they returned to the control level after 30 minutes and remained at that level throughout the rest of the experiment (10 days). This fact indicates that feedback mechanisms which control renin secretion, such as free plasma angiotensin II concentrations, are in the normal range. We therefore concluded that the renin-angiotensin system in antibody-injected rats was regulated at a normal level. Similar conditions seemed to exist in rabbits actively immunized against angiotensin II; these animals exhibited high concentrations of total immunoreactive angiotensin II (up to 200,000 pg/ml) and a small increase in plasma aldosterone and corticosterone concentrations.
Chronic one-kidney hypertension in rabbits. I. Treatment with kidney extracts.
Authors: Skeggs L T , Kahn J R , Levine M , Dorer F E , Lentz K E
Published: June 2012

An investigation into the mechanism that sustains the blood pressure in chronic one-kidney hypertension in rabbits was made using passive and active immunization with hog kidney extracts containing renin and with angiotensin antagonists. Seven hypertensive rabbits were passively immunized for extended periods with antiserum prepared in other rabbits. Antirenin levels were in the range of 1-3 units/ml. Control experiments demonstrated that antirenin concentrations of 1.0 unit/ml or more eliminated more than 99% of the pressor response to renin. There was no lowering of blood pressure that could be attributed to the antibodies. No decrease in blood pressure was observed in 13 experiments in 7 rabbits given the angiotensin II antagonist 1-Sar-8-Ile-angiotensin II; infusion rates of 0.09-87 mug/min kg-1 were used for periods of a few hours up to 3 days. A reduction in blood pressure occurred in 16 of 19 rabbits immunized directly with extracts containing renin with specific activities of 9.6-757 GU/mg. Plasma antirenin titers correlated poorly with reductions in blood pressure. The blood pressure of 22 rabbits given equal amounts of protein without renin was unaffected. It is concluded that the elevation of blood pressure in rabbits with chronic one-kidney hypertension is not dependent on ciculating renin or angiotensin; rather, it results from the presence of renin in an extravascular location or from an unknown pressor substance.
Pressure-flow and pressure-volume relations in the entire pulmonary vascular bed of the dog determined by two-port analysis.
Authors: Shoukas A A
Published: June 2012

To quantify the resistance and particularly the capacitance properties of the entire pulmonary vascular bed, isolated perfused lungs of nine dogs were studied. In each dog, with a fixed endotracheal pressure of 5 mm Hg, the arterial pressure-flow and pressure-volume relations were determined while venous pressure was fixed at constant values of 2, 5, and 8 mm Hg. In the same dogs, the venous pressure-flow and pressure-volume relations were also obtained when arterial pressure was fixed at constant values of 15 and 20 mm Hg. The arterial and venous pressure-flow relations could be regarded as linear around the physiological ranges of arterial and venous pressures; however, at very low pressures, these relations became nonlinear. The arterial and venous pressure-volume relations were also approximately linear within the physiological pressure ranges. The mean arterial compliance was 0.1798 ml/mm Hg kg-1 and was independent of venous pressures. The venous compliance values were 0.1236 and 0.0955 ml/mm Hg kg-1 for arterial pressures of 15 and 20 mm Hg, respectively. The sums of the arterial and venous compliances were 0.3034 and 0.2753 ml/mm Hg kg-1 for arterial pressures of 15 and 20 mm Hg, respectively. These values were nearly identical to the mean total compliance, 0.3265 ml/mm Hg kg-1, measured in a separate series of experiments in the same dogs. Therefore, the data obtained in these experiments using two-port analysis techniques represent the compliances and the resistance of the entire pulmonary vascular bed around the normal operating pressures and flows.
Electron microscopic immunohistochemical identification of endothelial cells in the rabbit.
Authors: Stemerman M B , Pitlick F A , Dembitzer H M
Published: June 2012

Antibody to tissue factor apoprotein was adsorbed against gamma-globulin and coupled to horseradish peroxidase; this complex was applied to various rabbit tissues. The distribution of the peroxidase marker then was observed by electron microscopy. We examined fixed or frozen sections, as well as breis of aorta, vena cava, brain, heart, lung, liver, spleen, kidney, bone marrow, mesothelial gut lining, erythrocytes, and platelets. All endothelial cells that had been exposed to the antibody complex were positive and in all cases only the endothelial cells showed localization of the electron-dense reaction product. Tissues that had been incubated with complexes prepared with gamma-globulin from animals not immunized with tissue factor apoprotein showed no staining. Prior treatment of the tissue with uncoupled anti-tissue factor gamma-globulin blocked binding by the coupled antibody. In blood vessel preparations that had been specifically designed to expose the media to the anti-tissue factor complex, medial smooth muscle cells and connective tissue showed no reaction product. Parenchymal cells of the other other organs mentioned likewise were devoid of reaction product. Similarly, the leukocytes and platelets occasionally observed in vessel lumens showed no evidence of binding. Platelets adhering to arterial subendothelial structure after injury also were unreactive. These findings suggest that in normal rabbits anti-tissue factor-horseradish peroxidase complex combines selectively with endothelial cells.
Vascular responses to arachidonic acid in the perfused canine lung.
Authors: Wicks T C , Rose J C , Johnson M , Ramwell P W , Kot P A
Published: June 2012

We compared the effects of arachidonic acid (AA), the bisenoic prostaglandin precursor, with those of prostaglandin F2a (PGF2a) and norepinephrine (NE) on pulmonary vascular resistance in the isolated (in situ), perfused canine lung lobe. The isolated lobe was perfused with autologous blood or an artificial perfusate under conditions of constant flow. Lobar artery and venous pressures were constantly monitored after bolus injections of AA, PGF2a, and NE into the inflow cannula. AA (100 mug/kg produced a significant increase in the pressure gradient (93.3 +/- 8.4%, SE) in the lobe. Similarly, PGF2a (1 mug/kg) significantly increased the pressure gradient (41.2 +/- 6.5%), as did NE (1 mug/kg, 41.6 +/- 3.2%). Aspirin (25 mg/kg) completely blocked the pulmonary vascular effect of AA, but did not affect the response to PGF2a, Linoleic acid, a control fatty acid, did not produce pulmonary vasoconstriction. The pressor effect of AA was not blocked by pretreatment with phentolamine, propranolol, cyproheptadine, or atropine. The use of an artificial perfusate free of cellular elements did not prevent the vasoconstrictor action of AA. The times to onset of action of the three agents were similar, and short. These results suggest that AA is converted into vasoactive intermediates or a prostaglandin, and the vasoactive intermediates or the prostaglandin act directly on precapillary pulmonary vascular smooth muscle rather than through platelet, plasma, adrenergic, or cholinergic mechanisms.
Depletion of cardiac norepinephrine during two forms of hemolytic anemia in the rat.
Authors: Swann J W , Contrera J F
Published: June 2012

Knowledge of the status of cardiac norepinephrine (NE) during anemia could lead to a better understanding of the role the sympathetic nervous system plays in cardiac function during anemia. Rats were made anemic by treatment with phenylhydrazine (PHZ). After the rapid onset of anemia, 60% of the stored NE in the heart was lost within 48 hours after treatment. Associated with the loss of cardiac NE was an increase in the wet weight of the heart, which reached a value 40% above control 48 hours after treatment. PHZ itself probably does not directly mediate this depletion of NE, since the vas deferens, brain and spleen had a normal store of NE at 48 hours. This contention was supported when rats, treated with PHZ, were transfused with normal rat red blood cells. This transfusion resulted in PHZ-treated rats which were not anemic. The hearts of these rats were not depleted of NE, but the hearts of the nontransfused, PHZ-treated controls were. Anemia also was induced by treating rats with anti-rat red blood cell serum. The hearts of these rats also were depleted of NE. These experiments show that during two forms of anemia there is a loss of NE from the sympathetic neurons innervating the heart. The effect of this on regulation of cardiac function remains to be determined.
Electrophysiological and antiarrhythmic effects of propranolol in canine acute myocardial ischemia.
Authors: Kupersmith J , Shiang H , Litwak R S , Herman M V
Published: June 2012

To correlate the antiarrhythmic and electrophysiological effects of propranolol in acute myocardial ischemia, we examined the effects of temporary (15-minute) ligations of the left anterior descending coronary artery in studies on 15 dogs. We recorded bipolar electrograms and monophasic action potentials from the ischemic and normal zones and measured the intervals from the onset of QRS in a standard electrocardiogram lead to the major deflection of electrograms recorded from the ischemic and normal zones. We also determined monophasic action potential duration (APD) and effective refractory period (ERP). Data for control ligations were compared to those during which propranolol, 40 mug/kg, was administered intravenously immediately after ligation. Propranolol reduced the mean number of ventricular beats per minute (from 15 to 6) (P less than 0.01). Propranolol slowed conduction in the ischemic zone (by 10 msec at peak effect, P less than 0.01) and had no or only a very slight effect (by 1-msec at 15 minutes, P less than 0.05) on conduction in the normal zone. Propranolol also prolonged APD in the ischemic (32-msec) and normal (14-msec) zones (P less than 0.01), prolonged ERP in the ischemic (41-msec) and normal (20-msec) zones (P less than 0.01), and reduced the APD/ERP ratio in the ischemic (1.62 to 1.47) (P less than 0.01) and normal (1.62 to 1.55) (P less than 0.05) zones. During the control ligation, APD in the ischemic zone was 25 msec shorter than in the normal zone (P less than 0.01), but with propranolol the difference was not significant. The effects of propranolol in slowing conduction in the ischemic zone, in prolonging refractoriness, in reducing APD/ERP, and in reducing the disparity in APD between ischemic and normal zones may explain its demonstrated antiarrhythmic effects in acute myocardial ischemia.
The effects of altered sodium balance and adrenergic blockade on renin release induced in rats by angiotensin antagonism.
Authors: Keeton T K , Pettinger W A , Campbell W B
Published: June 2012

Circulating angiotensin II is said to inhibit renin release by a direct, intrarenal action. This effect of angiotensin was studied indirectly using the selective angiotensin II antagonist saralasin (1Sar-8-Ala-angiotensin II) in conscious normal, sodium-depleted, and sodium-loaded rats. Saralasin caused a dose-related increase in plasma renin concentration (PRC) in normal and sodium-depleted rats, but had no effect on PRC in sodium-loaded animals. However, saralasin was 300 times more active in sodium-depleted rats than in normal rats. Saralasin caused hypotension and tachycardia in sodium-depleted rats, but not in normals. Propranolol inhibited saralasin-induced renin release by 99% in normal rats and by 75% in sodium-depleted rats but not alter the hypotensive effect of saralasin in the latter. Saralasin potentiated phentolamine-induced renin release, hypotension, and tachycardia in normal rats, and this potentiated renin release was blocked by propranolol. We conclude that a portion of saralasin-elicited renin release in sodium-depleted rats is mediated by hypotensive activation of the carotid baroreceptor reflex which increases sympathetic nervous activity in the kidney. However, in sodium-depleted rats saralasin induced a 42-fold increase in PRC, whereas an equipotent hypotensive dose of the vasodilator hydralazine caused only a 3.5-fold increase in PRC. Thus, we find that saralasin appears to have a selective effect on renin release over and above its hypotensive effect, which suggests an angiotensin-mediated, feedback mechanism inhibitory to renin release. Thus, we have come to the conclusion that for part of saralasin-induced renin release appears to be caused by disinhibition of angiotensin suppression of renin secretion. This "short-loop" feed-back mechanism is closely associated with intrarenal beta-adrenergic receptors, since propranolol impaired saralasin-induced renin release under all circumstances in our experiments.
Continuous determination of beat to beat stroke volume from aortic pressure pulses in the dog.
Authors: Bourgeois M J , Gilbert B K , Von Bernuth G , Wood E H
Published: June 2012

Present methods for measurement of stroke volume from the aortic pressure pulse are not suitable for beat-to-beat determinations during non-steady state conditions because these methods assume that each systolic ejection is equal to the peripheral runoff during the same beat. We have tested a new method which allows determination of an aortic pressure-volume conversion factor over a wide range of pressures during transient changes in stroke volume and infusions of vasoactive drugs in 6 dogs with chronically implanted aortic electromagnetic flowmeters. Each aortic diastolic pressure decay is approximated by an exponential the time constant of which is used to calculate the pressure loss during systole due to blood flow into the periphery. The total increment in aortic pressure due to systolic ejection, if there were no flow from the aorta during systole, then is calculated. The total systolic increment (delta PSV) is assumed to describe the pressure-volume characteristics during systole and is related to stroke volume by a constant multiplier that is derived from the indicator-dilution measurements of cardiac output. The values for beat-to-beat variations that were determined by use of the aortic electromagnetic flowmeter and by this aortic pressure pulse method were found to be within the range of measurement errors of stroke volume determined from individual aortic electromagnetic flow pulses.
Physiological loading of isolated mammalian cardiac muscle.
Authors: Paulus W J , Claes V A , Brutsaert D L
Published: June 2012

Cat papillary muscles were subjected to a complex loading function resulting from an analysis of the heart as a pump. The papillary muscle was assumed to be a hypothetical bundle of circumferential muscle fibers in the wall of a simplified cylindrical ventricle. The loading included inertial, resistive, and capacitive components of the cardiovascular system. Changes of ventricular dimensions were taken into account by application of a Laplace relationship. When this complex dynamic loading function was imposed on a shortening muscle by means of an electromagnetic feedback system, the developed force continuously changed with time. The time course of this changing force corresponded to the time course of calculated stress in the intact ejecting heart. Directly displayed force-velocity loops also were similar to loops obtained for the intact heart. Loads proportional to velocity of shortening (damping), acceleration of shortening (inertia), and to the square of shortening velocity (Bernoulli) were investigated separately. Cardiac muscle appeared rather insensitive to inertial loads, and the contribution of inertial loads in the early phase of a contraction under physiological pump loading was minimal. Moreover, during all these dynamic loadings, as long as loading was dynamically increasing or decreasing, velocity of shortening was respectively lower or higher at any muscle length and total load, when compared to velocity at the same length and load under static (constant preload and afterload only) loading.
Action potentials in chick atria. Ontogenetic changes in the dependence of tetrodotoxin-resistant action potentials on calcium, strontium, barium.
Authors: Pappano A J
Published: June 2012

Action potentials were recorded from chick embryo atrial muscle cells bathed in Tyrode's solution. Tetrodotoxin (TTX), 3.1 muM, was added to block the early, transient, Na+-dependent conductance system. Rectangular stimuli were used to evoke action potentials the peak amplitude (Ep) of which depend on the external concentration of divalent cations, [Me2+]0. The relationship between Ep and [Me2+]0 shifted to the right with increasing age. For example, the slope of Ep was 33 +/- 2,22 +/- 1 and 11 +/- 3 mV per 10-fold change in [Ca2+]0 on the 9th, 12th, and 18th incubation days, respectively. In solutions with reduced [Ca2+]0, Ep increased when Ba2+ or Sr2+ was added to the bath. The potency of Me2+ in generating action potentials was Ba2+ greater than Sr2+ greater than Ca2+ and this sequence did not change during development. Action potential amplitude, which was reduced in 18-day preparations, was increased by isoproterenol (increased Ca2+ conductance, gCa2+) and by tetraethylammonium (TEA) ion (decreased K+ conductance, gK). The results show that (1) Me2+-dependent action potentials support membrane excitation in chick atrial cells treated with TTX, and (2) the ability of Me2+ to support action potentials decreases during ontogenesis. We conclude from these experiments that the ontogenetically related decrease in Me2+-induced action potentials is the result of a reduction in gMe2+/gK+ during stimulation.
Influence of 5- and 6-hydroxydopamine on adrenergic transmission and nerve terminal morphology in the canine pulmonary vascular bed.
Authors: Kadowitz P J , Knight D S , Hibbs R G , Ellison J P , Joiner P D , Brody M J , Hyman A L
Published: June 2012

We studied the effects of 5- and 6-hydroxydopamine on adrenergic neurotransmission, fluorescence histochemistry, and nerve terminal ultrastructure in the canine pulmonary vascular bed. Fluorescence histochemistry on stretched preparations and sections of intrapulmonary artery and vein demonstrated that these vessels are well supplied with adrenergic nerves electron microscopy revealed adrenergic terminals in the adventitia and outer third of the media in the artery, but only in the adventitia in the vein. Adrenergic terminals in artery and vein contained many small and a few large dense-core vesicles. At least 20% of the terminals in the artery contained many small agranular vesicles and a few large opaque vesicles; this suggests that they were of the cholinergic type; Such terminals were not found in intrapulmonary veins. Under conditions of controlled blood flow, stimulation of the sympathetic nerves to the lung and intralobar injection of norepinephrine increased pressure in the perfused lobar artery and small intrapulmonary vein in a stimulus-related manner. The rise in pressure in the lobar artery and vein in response to nerve stimulation was blocked after administration of either 5- and 6-hydroxydopamine; Neither agent modified the response of the pulmonary vascular bed to norepinephrine; In contrast, the rise in pressure in the lobar artery and vein in response to both norepinephrine and to nerve stimulation was blocked by phenoxybenzamine, an alpha-receptor blocking agent. The attenuated neurogenic vasoconstrictor response in dogs treated with 5- and 6-hydroxydopamine was associated with a marked decrease in intensity of fluorescence of the abundant adrenergic innervation in both intrapulmonary artery and vein, and with the appearance of an osmiophilic material in dense-core vesicles of adrenergic terminals in artery and vein. We believe that these data suggest that 5- and 6-hydroxydopamine interfere with adrenergic transmission in intrapulmonary vessels by depleting norepinephrine from adrenergic terminals. Furthermore, we conclude from hemodynamic, histochemical, and ultrastructural studies that vasomotor tone in the pulmonary vascular bed can be regulated by the sympathetic nervous system.
Renin release by rat kidney slices incubated in vitro. Role of sodium and of alpha- and beta-adrenergic receptors, and effect of vincristine.
Authors: Capponi A M , Vallotton M B
Published: June 2012

The role of sodium concentration, of alpha- and beta-adrenergic receptors, and of a microtubular inhibtor (vincristine) on renin release was studied in rat kidney slices in vitro. Renin release was an active, linear, and temperature-dependent process. Kidneys from young rats released much more renin than those from adults. Lowering sodium concentration inhibited renin release by one-half, even when osmolality was kept constant. Isoproterenol (10(-8) to 10(-5) M) stimulated renin release significantly in a partially dose-related manner. dl-propranolol inhibited this stimulation. Significant (P less than 0.05) inhibition of renin release was induced by l-epinephrine or l-norepinephrine (10(-5) M). In the presence of an alpha-receptor blocking drug, phenoxybenzamine (10(-5) M), inhibition no longer occurred with epinephrine and stimulation was observed with l-norepinephrine. Vincristine (10(-5) M) did not affect renin release when slices from the kidneys of normal rats or adrenalectomized, sodium-depleted rats were incubated, but significantly inhibited (P less than 0.01) release that had been stimulated in vitro by isoproterenol. These results suggest to us that there may be (1) a direct or indirect (mediated through the macula densa) effect of sodium on juxtaglomerular cells, (2) an inhibitory role for alpha-adrenergic receptors on renin release, in addition to the stimulatory role of beta-receptors, (3) possible participation of microtubules in isoproterenol-stimulated renin release, and (4) an alternative mode of secretion of renin under stimulation by adrenalectomy and salt depletion.
Collecting duct function in deoxycorticosterone acetate-escaped, normal, and salt-deprived rats. Response to hypervolemia.
Authors: Sonnenberg H
Published: June 2012

The microcatheterization technique was used to study reabsorption of fluid, sodium, and potassium in the medullary collecting duct in chronically deoxycorticosterone acetate (DOCA)-treated and salt-loaded rats, as well as in normal and chronically salt-deprived (NaD) rats, before and after infusion of donor blood (33% of estimated circulating volume). Before expansion, urinary sodium excretion was highest in DOCA rats, intermediate in normal, and lowest in low salt rats. Significant collecting duct reabsorption was found in NaD, normal, and DOCA groups. In contrast to sodium, no net transport of potassium was found in any series. During intravascular expansion, increased renal excretion of fluid and sodium was observed uniformly in both DOCA and normal groups, whereas a diuretic response was found in five of seven rats, and a natriuretic response in four of seven rats of the NaD group. Natriuresis of DOCA rats was significantly greater than that of either normal or responding NaD rats. Diuresis and natriuresis in all three series were assocaited with complete inhibition of fluid and sodium reabsorption from the lumen of the medullary collecting duct, whereas such reabsorption persisted in nonresponding low salt rats. Increased sodium excretion in DOCA rats in comparison to the other two series could be explained by enhanced intratubular delivery of the ion to the medullary collecting system. I conclude that the renal response to acute blood volume expansion is due primarily to complete inhibition of both fluid and sodium reabsorption in the medullary collecting duct, but that differences in tubular delivery may modify the resulting diuresis and natriuresis.
Quantification of collateral resistance in acute and chronic experimental coronary occlusion in the dog.
Authors: Schaper W , Flameng W , Winkler B , Wüsten B , Türschmann W , Neugebauer G , Carl M , Pasyk S
Published: June 2012

The resistance to coronary blood flow in various parts of the myocardium was studied with the tracer microspheres technique before and immediately after an acute coronary occlusion and several weeks after a more slowly occurring coronary occlusion by Ameroid constrictor. All experiments were carried out in the isolated, metabolically supported, empty, beating dog heart at maximal coronary vasodilation induced with adenosine. Coronary resistance of the normal empty beating heart at maximal coronary vasodilation was 0.20 mm mm Hg/(ml/min) per 100 g of tissue (subepicardium) and 0.16 mm Hg/(ml/min) per 100 g of tissue (subendocardium). After acute coronary occlusion the perfusion of the subtended myocardium was maintained at a much lower level by way of collateral vessels, which showed a resistance to flow of 3.52 mm Hg/(ml/min) per 100 g. If coronary artery occlusion proceeded more slowly the collateral vessels became more functional and myocardial infarction was avoided. During collateral enlargement collateral resistance fell from 3.52 to 0.22 mm Hg/(ml/min) per 100 g within a period of 8 weeks after implantation of the constricting device. The degree of compensation by collaterals for the loss of the occluded native coronary artery was 33% of its former conductance.
Age-related changes in ouabain pharmacology. Ouabain exhibits a different volume of distribution in adult and young dogs.
Authors: Glantz S A , Kernoff R , Goldman R H
Published: June 2012

To better understand why one must administer much higher doeses of digitalis glycosides to immature than to mature humans and animals, we studied ouabain pharmacokinetics in adult and young dogs. Consistent with reported observations that ouabain-binding, metabolism, and excretion do not change with age, we found no significant differences in the transfer coefficients in a linear two-compartment open model for ouabain pharmacokinetics following a bolus of 0.05 mg/kg. We did find, however, that young dogs had nearly twice the ouabain volumes of distribution per kilogram of body weight as adults (155.4 +/- 1.2 (SE) ml/kg vs. 80 +/- 0.6, P less than 0.0005) and that one could account for this difference with the fact that young dogs had nearly twice the plasma volume 108 +/- 9.8, vs. 68 +/- 7.3, P = 0.001) and interstitial fluid space (318 +/- 35 vs. 190 +/- 6.5, P = 0.006) as the adults. For the same dose per kilogram, left and right ventricular ouabain concentrations were inversely related to the volume of distribution, with the adults having significantly higher tissue levels and incidence of arrhythmias. One must give more ouabain to a young dog to get the same plasma concentration as in an adult because the mass of ouabain in rapid equilibrium with the plasma is diluted in a larger volume of distribution.
Effects of cardiac sympathetic stimulation and ablation of canine ventricular anodal strength-interval curves.
Authors: Burgess M J , Levine H J
Published: June 2012

We studied the effects of cardiac sympathetic stimulation and ablation on characteristics of the anodal-strength interval curve in 10 pentobarbital-anesthetized open-chest dogs. We gave special attention to the form and particularly the depth of early dips of the anodal strength-interval curve. When the central connections of the cardiac sympathetic nerves were intact, left stellate stimulation decreased threshold for excitation during the dip only slightly (from 883 +/- 442 muA to 774 +/- 326 muA P less than 0.1). However, after left stellectomy and upper thoracic ganglionectomy, stimulation of the cut ends the ansa subclavia decreased the dip threshold from an average of 952 +/- 321 muA to 707 +/- 210 muA, A less than 0.01. Dip thresholds in strength-interval curves determined 1-1.5 hours after ganglionectomy average 1164 +/- 296 muA compared to an average dip threshold of 791 +/- 269 muA in strength-interval curves measured immediately prior to stellectomy. This increase is statistically significant (P less than 0.005). In addition to the effects of sympathetic tone on disparity of refractory period and ventricular fibrillation threshold, the effects of sympathetic tone on the form of the strength-interval curve may be another factor influencing vulnerability to arrhythmias and particularly in patients with abnormal autonomic tone.
Effect of variation in dietary NaCl intake on total and fractional renal blood flow in the normal and mercury-intoxicated rat.
Authors: Lameire N , Ringoir S , Leusen I
Published: June 2012

We studied the effect of different chronic (3-4 weeks) dietary salt intakes on intrarenal hemodynamics of normal and mercury-intoxicated rats. Cardiac output (CO), total renal blood flow (RBF), and the zonal perfusion rate in the outer cortex (OC) and inner cortex (IC) were measured by the radioactive microsphere method. The distribution of cortical blood flow was calculated as the distribution index (DI), which reflects the ratio OC/IC. Rats were placed on a high salt diet (group I), intermediate salt diet (group II), or low salt diet (group III). For each group control rats (subgroup A) and mercury-intoxicated rats (subgroup B) were studied. No effect of the different salt intakes on the DI could be detected. The DI in group IA was 2.35 +/- 0.14; in IIA, 2.40 +/- 0.16; and in IIIA, 2.38 +/- 0.09 (P greater than 0.05). After mercury injection RBF changed from 5.32 +/- 0.36 ml/g.min(-1) (IIA) to 3.31 +/- 0.20 ml/g.min(-1), IIB and from 4.32 +/- 0.11ml/g.min(-1) (IIIA) to 1.98 +/- 0.10 ml/g.min(-1) (IIIB) P less than 0.01). The DI was lowered to 1.53 +/- 0.06 (IIB) (P less than 0.05) and to 1.16 +/- 0.10 (IIIB) (P less than 0.01). In both IIB and IIIB a marked elevation of the blood urea was noted (IIB = 97 +/- 9 MG/100 ML AND IIIB = 182 +/- 25 mg/100 ml). In group IB no effect on RBF, OC, IC, or DI could be observed (for all values, P greater than 0.05) despite similar histological renal lesions. Group IB rats also had normal blood urea levels (31 +/- 6 mg/100 ml;P greater than 0.05). We conclude (1) that variations in dietary salt intake appear to have no detectable effect on the intracortical blood flow distribution; and furthermore (2) that the mercury-induced acute renal failure (ARF) is characterized hemodynamically by a total renal and preferential outer cortical ischemia and that chronic salt loading prevents the ARF while preserving normal renal perfusion.
beta-adrenergic blockade in essential hypertension: reduced renin release despite renal vasoconstriction.
Authors: Sullivan J M , Adams D F , Hollenberg N K
Published: June 2012

The acute effects of small doses of intravenous propranolol on renin release and on circulatory dynamics were studied at the time of renal arteriography in 12 persons with essential hypertension. All of the subjects had a normal peripheral renin response to chronic sodium depletion and all had normal renal function. Seven subjects received a 10-mEq sodium diet. At the time of arteriography, arterial blood pressure, pulse rate, cardiac output, renal blood flow, and arterial and renal venous renin activity were measured before and 6-20 minutes after the intravenous administration of propranolol (9-18 mjg/kg). Average renin secretion rate in the salt-depleted subjects fell from 367 +/- 80 (SEM) U/ml per 100 g/min to 122 +/- 51 U/ml per 100 g (P=0.03) and renal plasma flow fell from 189 to 155 ml/min per 100 g (P = 0.018). We also found that in the salt-loaded subjects, renal plasma flow fell from 213 to 184 ml/min per 100 g (P = 0.025), whereas renin secretion did not change significantly in either group. We conclude that propranolol rapidly blocks renin release despite circulatory changes which ordinarily constitute a stimulus for renin secretion, i.e., renal vasoconstriction and reduced renal blood flow.
The effect of prostaglandin A1 on renin and aldosterone in man.
Authors: Golub M S , Speckart P F , Zia P K , Horton R
Published: June 2012

Blood pressure, pulse rate, plasma aldosterone (PA), renin, and cortisol were monitored during graded intravenous infusions of prostaglandin At (PGA)1), 0.075-0.6 mug/kg min-1, alone and superimposed on angiotensin II (A II) administration in five normal men. The infusions of PGA1 did not affect blood pressure, but did progressively increase the pulse rate up to 15.2 +/- 2.0 (SEM- beats/min at the highest prostaglandin dose (0.6 mug/kg min-1). Both PA and plasma renin activity (PRA) increased in a dose-related fashion in response to the prostaglandin infusions. Aldosterone increased from a control of 4.8 +/- 0.4 to 20.7 +/- 1.2 ng and PRA increased from 0.9 +/- 0.1 to 5.4 +/- 0.4 ng/ml hr-1 at the dose of 0.6 mug/kg min-1. The correlation between the aldosterone and renin values was r = 0.85 P less than 0.001. In separate experiments, acute volume expansion with 2 liters of saline did not affect the increase in renin activity induced by exogenous prostaglandin. A II (5 ng/kg min-1) increased aldosterone and blood pressure and decreased the pulse rate. The hemodynamic effects were progressively reversed by the superimposed prostaglandin infusions, but the observed changes in renin and aldosterone concentrations were not further altered. The PA response to A II infusions was not influenced by indomethacin pretreatment. Prostaglandin A (infusion) appears to have a direct effect on renin release in man.
Substrate specificity of tonin from rat submaxillary gland.
Authors: Schiller P W , Demassieux S , Boucher R
Published: June 2012

The substrate specificity of tonin from rat submaxillary gland was examined with a series of synthetic peptides encompassing the C-terminus of the decapeptide substrate angiotensin I. In contrast to angiotensin I-converting enzyme from plasma or lung, only angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I are substrates of tonin with Km values of 34.5 muM, 39.3 muM, and 54.4 muM, respectively, while the shorter C-terminal peptides are not hydrolyzed. Thus, the N-terminal sequence extending from position 1 to 3 is the enzymatic binding site for tonin. Turnover numbers of 33.4 sec-1, 42.8 sec-1, and 6.5 sec-1 are observed for the hydrolysis of angiotensin I, (des-Asp1)-angiotensin I, and (des-Asp1, des-Arg2)-angiotensin I, respectively. The relative percentage rates of hydrolysis (proportional to V/Km) at low substrate concentrations ([S] less than less than Km) are almost identical for (des-Asp1)-angiotensin I, angiotensin I, and the tetradecapeptide substrate, indicating that these three peptides are equally good substrates at low physiological concentrations. The observed high specificity of the enzyme lends support to the possible important role of tonin for local conversion in tissue. The conversion of (des-Asp1)-angiotensin I to (des-Asp1)-angiotensin II (angiotensin III) is of particular interest in relation to the recently suggested, potential role of the latter peptide in aldosterone release.