bluuebunny/crossref_metadata_2025 huggingface dataset:
Central and peripheral adrenergic mechanisms in the development of deoxycorticosterone-saline hypertension in rats.
Authors: Reid J L , Zivin J A , Kopin I J
Published: June 2012

The role of the sympathetic nervous system in the development of deoxycorticosterone-sodium chloride (DOCA-saline) hypertension was investigated by measuring plasma levels of norepinephrine, total catecholamines, and dopamine-beta-hydroxylase activity at intervals after the initiation of the DOCA-saline regimen. Plasma norepinephrine was significantly higher in DOCA-saline-treated rats at 4 and 7 weeks and in rats treated with saline alone at 4 weeks compared with that in untreated controls. Total plasma catecholamine levels (epinephrine and norepinephrine) and dopamine-beta-hydroxylase activity were similar in hypertensive rats, untreated controls, and rats that received either DOCA or saline alone. The increases in plasma norepinephrine levels may have resulted from centrally mediated increases in peripheral sympathetic neuronal activity, since the destruction of central catecholaminergic neurons with intracerebroventricularly administered 6-hydroxydopamine (6-OHDA) prevented both the DOCA-saline-induced rise in blood pressure and the increases in plasma norepinephrine. Rats treated with 6-OHDA consistently drank less water or saline than did vehicle-treated controls. The actions of centrally administered 6-OHDA on blood pressure and plasma norepinephrine levels were not secondary to a reduction in salt intake, however, since intact rats given a similar reduced saline intake became hypertensive and demonstrated elevated plasma norepinephrine concentrations. Chronic salt loading may cause a centrally mediated increase in peripheral sympathetic neuronal activity with raised plasma concentrations of norepinephrine. The increased adrenergic activity in the presence of mineralocorticoid-induced sodium retention leads to the development of hypertension.
Increased sheep lung vascular permeability caused by histamine.
Authors: Brigham K L , Owen P J
Published: June 2012

To see whether histamine increases lung vascular permeability to protein, we compared the effects of steady-state histamine infusions on lung vascular pressures, lung lymph flow, and lung lymph protein content with the effects of mechanically elevated lung vascular pressures on these variables in the same unanesthetized sheep. We surgically implanted catheters in the pulmonary artery, the left atrium, the superior vena cava, and a main lung lymphatic. After the sheep had recovered from surgery, we carried out steady-state experiments without anesthesia. Histamine induced a dose-related, quickly reversible increase in lung lymph flow without affecting pulmonary artery pressure, and it caused left atrial pressure to fall. During 4-hour intravenous 4-mug/kg min-1 histamine infusions, lymph flow and lymph protein clearance (lymph flow X lymph-plasma protein concentration ratio) increased more than they did with mechanically elevated pressure even though vascular pressures fell. Lymph-plasma protein ratios decreased linearly with increasing lymph flow during increased pressure experiments, but during histamine infusions the ratios did not decrease even though lymph flow increased 2-6-fold. Lymph clearance and permeability-surface area products (PS) for eight protein fractions with molecular radii ranging from 36 to 100 A decreased with increasing molecular size in base-line, increased pressure, and histamine studies. PS values for all eight fractions were significantly higher than base line in histamine experiments but not in increased pressure experiments. Four-hour intravenous histamine infusions caused moderate increases in lung water content. Left atrial infusions had less effect on lymph flow than did intravenous infusions. We conclude that histamine causes pulmonary vascular permeability to protein to increase but that the effects on exchanging vessel porosity are more modest than those suggested for systemic microvessels. Histamine should be considered a possible mediator of increased lung vascular permeability.
Triggered activity in cardiac muscle fibers of the simian mitral valve.
Authors: Wit A L , Cranefield P F
Published: June 2012

The action potential of cardiac fibers in the anterior mitral valve leaflet of the monkey heart is followed by an after-hyperpolarization. The addition of catecholamines causes a delayed after-depolarization to follow the after-hyperpolarization. The amplitude of the after-depolarization increases as the stimulus cycle length is decreased, or after premature stimulation, and as a result can reach threshold to yield nondriven, sustained rhythmic activity which we term triggered activity. This sustained rhythmic activity can be terminated by a single, appropriately timed, premature stimulus. The amplitude of the action potentials of mitral valve fibers is increased by catecholamines; the amplitude and rate of depolarization are depressed by verapamil. The amplitude of the action potentials is little affected by tetrodotoxin (TTX) but the maximum rate of depolarization is reduced by TTX. The delayed after-depolarization induced by catecholamines is abolished by verapamil, as is triggered activity. These observations suggest that mitral valve fibers generate slow response action potentials, that triggerable sustained rhythmic activity may be a property of the slow response and that such activity may cause the types of cardiac arrhythmias that usually are attributed to reentry.
Renal tubular transport of 3H-digoxin in saline diuresis in rats.
Authors: Roman R J , Kauker M L
Published: June 2012

We evaluated urinary excretion and tubular transport of 3H-digoxin by three different methods in anesthetized rats made diuretic by infusion of 2.5% saline. In one group small volumes of 3H-digoxin and 14C-inulin were injected simultaneously into surface proximal convolutions, and urine was collected serially from both ureters. Digoxin recovery was lower after early (62.1 +/- 5.3%) than after late (86.9 +/- 7.7%) proximal administration but inulin recovery was complete (99.6 +/- 2.7%) after all injections. Most of the digoxin was excreted simultaneously with inulin. Delayed recovery was low. In another group of rats digoxin and inulin were applied directly to the capsule of the left kidney. Two-thirds of the recovered digoxin appeared from the left ureter and one-third from the right. The difference (41.9 +/- 7.4%) is an estimate of transtubular digoxin influx. Digoxin excretion preceded inulin only on the left. Digoxin to inulin concentration ratios were 6 times higher from the left than the right, whereas inulin recoveries from the two sides were similar. In a third group of rats tubular fluid was collected from surface convolutions of proximal and distal tubule. In the accessible segment of the proximal tubule 35.9% of the filtered digoxin was reabsorbed. In the more distal nephron, drug was added into the lumen; this resulted in a net urinary excretion of 80.2 +/- 18.2%. These findings are compatible with free filtration of digoxin at the glomerulus followed by passive proximal tubular reabsorption and an influx against a concentration gradient in the distal nephron.
Afferent neural pathway in the regulation of cardiopulmonary responses to tissue hypermetabolism.
Authors: Liang C S , Hood W B
Published: June 2012

We studied the role of neural transmission from hypermetabolic peripheral tissues in the regulation of cardiac output and pulmonary ventilation in chloralose-anesthetized dogs. Cross-circulation techniques with femoral-femoral or femoral-aortic anastomoses were used to produce a vascularly isolated, but normally innervated, hindlimb or lower half-body, 2,4-Dinitrophenol (DNP) was infused into the arterial side of the perfusion circuit to triple oxygen consumption and to increase lactate production by the cross-perfused area. After infusion of DNP, cardiac output and mean systemic arterial blood pressure increased, but neither heart rate nor pulmonary artery wedge pressure changed significantly. Pulmonary minute ventilation and arterial pH also increased, while arterial PCO2 fell. These changes were abolished when the nerve connections between the perfused limb and its parent body were severed. Normal saline, when administered in a similar manner, did not increase either ventilation or cardiac output, and simple denervation without previous infusions of DNP also had no effect. These results indicate that there are receptors sensitive to metabolic changes in the tissue, and that neural transmission is an important afferent link in regulating the cardiopulmonary responses to increased tissue metabolism.
Effects on myocardial contractility of blood-borne material released from the feline small intestine in simulated shock.
Authors: Lundgren O , Haglund U , Isaksson O , Abe T
Published: June 2012

There is a pronounced derangement in cardiovascular function in the cat after a 2- or 3-hour period during which shock is simulated in the small intestine by regional hypotension (BP = 30-35 mm Hg) during activation of vasoconstrictor nerve fibers. It has been proposed that these effects are caused by blood-borne cardiode-pressant substance(s) released from the "shocked" small intestine. To obtain further evidence for this hypothesis we performed a study on two heart preparations in vitro. Rabbit papillary muscles or isolated beating rat hearts were exposed to intestinal venous plasma obtained from control cats and from cats subjected to simulated intestinal shock for 2 or 3 hours. while control plasma induced only a slight depression of myocardial contractility, plasma from "shocked" intestine caused a significant decrease in peak isometric tension of the papillary muscles or a fall in systolic pressure of the rat hearts. Since the experiments on papillary muscle indicated that time to peak tension was largely unaffected by the plasma samples, we conclude that the feline intestine in shock releases material into blood that exerts a negative inotropic effect on the myocardium.
Electrogenesis of increased norepinephrine sensitivity of arterial vascular muscle in hypertension.
Authors: Hermsmeyer K
Published: June 2012

The possibility that the vascular muscle cell might contribute to the development of essential hypertension by being more responsive to norepinephrine because of an inherently lower membrane potential (Em) was investigated. Experiments were designed to test the hypothesis that Em of arterial vascular muscle cells from spontaneously hypertensive rats (SHR) are less negative than those from matched Kyoto normotensive rats (KNR). The caudal artery, a muscular, densely innervated regulating artery 300-400 mum in outside diameter, which is activated by graded (nonspiking) depolarization to produce a maintained contraction, was studied. Vascular muscle cells from SHR always had less negative Em than those from KNR at 16 degrees C, but not at 36 degrees C, over a range of K+ concentrations from 2.7 mM to 150 mM. From the relationship between Em and K+ concentration, intracellular K+ concentration ([K+]i) was estimated to be 150 mM for SHR and 170 mM for KNR. The caudal artery undergoes a large depolarization when K+ is removed from the superfusing solution and a transient hyperpolarization that exceeds the calculated EK (potassium equilibrium potential) when K+ is replaced. The magnitude of the hyper-polarization on returning to 30 mM or 50 mM K+ always was greater for vascular muscle of SHR than KNR. The apparently lower [K+]i and more active (compensating) electrogenic ion transport in the SHR vascular muscle cells thus result in an unaltered Em at body temperature in the physiological range of K+ concentrations. However, depolarization by norepinephrine was greater over the middle of the dose-response curve, and this greater depolarization caused the contractions of SHR arteries to be greater. The altered electrogenesis of the SHR vascular muscle cells is postulated to provide a mechanism for the increased reactivity of arteries to norepinephrein in hypertension.
Role of resistance and exchange vessels in local microvascular control of skeletal muscle oxygenation in the dog.
Authors: Granger H J , Goodman A H , Granger D N
Published: June 2012

The effects of reduction in perfusion pressure, arterial hypoxia, muscle contraction, and adrenergic stimulation on the hindlimb muscle circulation were studied. Under normal conditions (venous PO2 greater than or equal to 40 mm Hg), oxygen delivery to the muscle was maintained mainly by large increases in the capillary exchange capacity and the oxygen extraction ratio in accord with tissue demand following the application of the above stresses. The participation of the resistance vessels under these conditions was minimal. The prevailing venous oxygen tension then was reduced by several means and the response of vascular resistance and capillary exchange capacity to the same stresses was reexamined. At the lower prevailing venous PO2, the sensitivity of the resistance vessels to metabolic and hemodynamic disturbances was greatly increased. Consequently, blood flow autoregulation, functional hyperemia, and hypoxic hyperemia were more intense when venous oxygen tension was low. In contrast, the contribution of exchange capacity was diminished, probably owing to the fact that most of the capillaries already are open at low venous PO2. These data suggest that the locus of local microvascular control of muscle oxygenation shifts from the normally more sensitive precapillary sphincters to the proximal flow-controlling arterioles as the prevailing venous oxygen tension falls. Yet, although the relative contribution of the resistance and exchange vessels to intrinsic regulation of tissue oxygenation is related to the prevailing venous oxygen tension, the two compensatory mechanisms operating in concert maintain tissue PO2 above the critical level over a wide range of stresses.
Experimental evidence for regional cardiac influence in body surface isopotential maps of dogs.
Authors: Abildskov J A , Burgess M J , Lux R L , Wyatt R F
Published: June 2012

Isopotential mpas based on 192-200 body surface electrocardiograms were obtained for 20 dogs during multiple patterns of ventricular activation. The purposes of the study were to determine whether the cardiac location of events responsible for surface potentials had a recognizable influence on surface potential patterns and to examine the influence of electrical events occurring simultaneously in multiple cardiac regions. Substantially different effects of electrical activity in various cardiac regions on body surface potentials were evidenced by the body surface location of potential maxima and minima and by patterns of isopotential lines during early portions of ventricular excitation initiated at different ventricular sites. Simultaneous stimulation at some sites gave surface potential distributions with multiple extrema. These were demonstrated to be due to effects of the different cardiac regions, because addition of potentials due to stimulation of the individual sites duplicated those associated with simultaneous stimulation of the same sites. It was also shown that body surface locations of maxima and minima are not related in the same manner to the cardiac location of the responsible events when these events are present in single and multiple regions. Slopes of potentials due to events in single cardiac regions were shown to combine with slopes produced by events in other regions to yield maxima or minima at new body surface locations. Results of the study support the possibility of regional cardiac examination by electrocardiography but suggest that this will require quantitative descriptions of the details of potential patterns in addition to the location of potential peaks.
Effects of acetylsalicylic acid on the ductus arteriosus and circulation in fetal lambs in utero.
Authors: Heymann M A , Rudolph A M
Published: June 2012

Intra-arterial and intravenous catheters were inserted in six fetal lambs at 125-130 days of gestation. On the following day, fetal arterial pressures and blood gases were monitored and fetal cardiac output and its distribution were measured by injection of radionuclide-labeled microspheres 15 mum in diameter. Acetylsalicylic acid, 55-90 mg/kg of estimated fetal weight, then was administered into the fetal stomach. Fetal pulmonary arterial pressure rose significantly after an average of 58 minutes, increasing the pressure difference between the pulmonary artery and the aorta from 2 +/- 0.3 (SEM) mm Hg during control to 11.2 +/- 1.6 mm Hg. Resistance across the ductus arteriosus rose from 4.2 +/- 0.5 (SEM) to 27.4 +/- 4.01 units, and flow fell from 495 +/- 44 (SEM) to 409 +/- 20 ml/minute. The proportion of combined ventricular output distributed to the placenta, adrenals, heart, and lungs increased, whereas the proportion of combined ventricular output distributed to the brain, liver, intestine, kidneys, and upper and lower body fell. In two fetuses infusion of prostaglandin E1 reversed the pulmonary hypertension. Inhibition of prostaglandin synthesis in fetal lambs produced constriction of the ductus arteriosus and redistribution of cardiac output. It is probable that prostaglandins, particularly E1, are involved in regulation of blood flow through the ductus arteriosus and various vascular beds in the normal resting fetus.
Role of heart and lung receptors with nonmedullated vagal afferents in circulatory control.
Authors: Thorén P N , Donald D E , Shepherd J T
Published: June 2012

Vagal afferents from the cardiopulmonary region exert a tonic inhibition on the vasomotor center. This is demonstrated by constriction of systemic resistance and splanchnic capacitance vessels and by increased output of renin when the vagi are cut or blocked. In dogs, removal or selective denervation of organs showed that receptors in the lungs, the atria, and the ventricles each are responsible for the vasomotor inhibition. That this inhibition is due to nonmedullated vagal afferents (C fibers) was demonstrated by selective cooling of the vagi, anodal block of medullated afferents, and selective electrical stimulation of medullated and nonmedullated fibers. In the open-chest cat the discharge frequency of individual C fibers is sparse and irregular (mean, 1.4 impulses/sec) but increases to 10 or more impulses/sec with moderate increases in cardiac filling pressure and exhibits cardiac rhythmicity or is continuous throughout the cardiac cycle. The inhibition of sympathetic vasomotor outflow effected through the cardiopulmonary receptors is inversely related to that exerted by the arterial baroreceptors. The former receptors have less influence on the muscle circulation than the latter, but have an equal or greater effect on the renal circulation. In summary, receptors in the heart and lungs with nonmedullated vagal afferents are an important component of the integrated neural control of the circulation.
Plasma cyclic adenosine 3':5'-monophosphate response to isoproterenol and glucagon in hyperkinetic borderline (labile) hypertension.
Authors: Messerli F H , Kuchel O , Hamet P , Tolis G , Guthrie G P , Fraysse J , Nowaczynski W , Genest J
Published: June 2012

The hemodynamic changes observed in patients with the "hyperkinetic" form of borderline (labile) essential hypertension (BEH) could be related to the hyperresponsiveness of cardiac beta-adrenergic receptors to catecholamines. The isoproterenol-induced increase in plasma cyclic adenosine 3':5'-monophosphate (cAMP) reflects the response of adenylate cyclase to beta-adrenergic stimulation, whereas a non-beta-receptor-mediated increase occurs with the administration of glucagon. Both substances were infused into 13 control subjects and 14 patients with the hyperkinetic form of BEH before and after propranolol administration. Baseline plasma cAMP concentrations were comparable in both groups. After 30 minutes of isoproterenol infusion (20 ng/kg per min) a significantly higher increase in plasma cAMP and heart rate and a smaller decrease in diastolic blood pressure were seen in this type of BEH than in control subjects. The increase in plasma cAMP and in heart rate correlated positively when all subjects were considered together. Propranolol abolished hemodynamic and humoral responses to a similar degree in both groups. The plasma cAMP responses to glucagon (200 ng/kg per min) were slightly lower in our patients with BEH than in control subjects and were not suppressed by propranolol. The data are compatible with a hyperreactivity of the beta-adrenergic receptors or of the adenylate cyclase or both in hyperkinetic BEH and could correspond to the previously observed exaggerated beta-adrenergic drive to the heart in this type of hypertension. The non-beta-receptor-mediated rise in plasma cAMP (glucagon), however, remains comparable in control subjects and BEH.
The relevance of peripheral baroreceptors and chemoreceptors to regulation of cerebral blood flow in the cat.
Authors: Bates D , Sundt T M
Published: June 2012

The contribution of neural vasomotor reflexes to the control of cerebral blood flow (CBF) was investigated in 30 cats lightly anesthetized with pentobarbital. CBF was measured both by kinetic analysis and by the intial slope technique of the washout curve of a bolus of 133Xe. Autoregulation (10 cats) and responsiveness to alteration in arterial PCO2 (PaCO2) (10 cats) and arterial PO2 (Pao2) (five cats) were assessed both before and after bilateral intracranial division of the 9th and 10th nerves. In an additional group (five cats), related changes in CBF to alteration of PaCO2 were recorded before and after unilateral section of the 7th and 8th nerves. Autoregulation was preserve after division of the 9th and 10th nerves and there was no significant change in the PaCO2 response curves. Section of the 7th and 8th cranial nerves did not produce conclusive results in the small number of cats studied. A conclusion that the facial nerves are not dominant in responses to hypercapnia seems justified, but a modulating role for these nerves is possible. These studies do not exclude a physiological role for these nerves in the autoregulation of CBF, but do indicate that the cerebral vascular bed apparently is capable of functioning normally after their division.
Regional cardiac prostaglandin release during myocardial ischemia in anesthetized dogs.
Authors: Berger H J , Zaret B L , Speroff L , Cohen L S , Wolfson S
Published: June 2012

Cardiac prostaglandin release was studied in closed-chest dogs during acute coronary occlusion. Aortic and coronary sinus blood was obtained before, and at intervals after, balloon occlusion of the left anterior descending artery in seven dogs. Samples were assayed for prostaglandins F, E, and A by randioimmunoassay. All dogs demonstrated prostaglandin F release, Mean +/- SE postocclusion aortic levels were 0.26 +/- 0.01 ng/ml; coronary sinus levels were 0.67 +/- 0.01 ng/ml (P less than 0.001). In six dogs, prostaglandin E also was released. Mean postocclusion aortic levels were 0.24 +/- 0.01 ng/ml; coronary sinus, 0.44 +/- 0.01 ng/ml (P less than 0.001). There was no release of prostaglandin A. To examine the site of prostaglandin release, simultaneous samples from the aorta, the coronary sinus, and the great cardiac vein were obtained before and after left circumflex artery occlusion in six additional studies. The great cardiac vein drained effluent from nonischemic myocardium, whereas the coronary sinus drainage included blood from both ischemic and nonischemic zones. All six dogs demonstrated prostaglandin F release from the ischemic region. Mean postocclusion aortic prostaglandin F was 0.32 +/- 0.01 ng/ml. Coronary sinus prostaglandin F was 1.69 +/- 0.03 ng/ml (P less than 0.001), whereas the great cardiac vein level remained at 0.34 +/- 0.01 ng/ml (P greater than 0.05). Prostaglandin E was released from both ischemic and nonischemic regions. Mean aortic prostaglandin E was 0.21 +/- 0.01 ng/ml; great cardiac vein, 0.55 +/- 0.02 ng/ml (P less than 0.001); and coronary sinus, 1.07 +/- 0.04 ng/ml (P less than 0.001). These results have led us to conclude that the different local availability of prostaglandins E and F may influence the cardiac response to ischemia.
Vessel caliber and branch-angle of human coronary artery branch-points.
Authors: Hutchins G M , Miner M M , Boitnott J K
Published: June 2012

Measurements were made of parent and branch vessel diameters and of the included angles of branch-points from postmortem human coronary arteriograms to determine the usefulness of theoretical equations predicting the relationships between parent and branch vessel caliber and between arterial caliber and branch-angle. The formulas were based on the concept that blood vessel size and arrangement provided for blood flow with minimum energy loss. Size relationships between parent vessel and its branches were determined for 42 left main and 53 other epicardial coronary artery branch-points in hearts with angiographically normal arteries. Left main coronary artery branch-points were studied in 68 hearts with various degrees of angiographically defined coronary artery disease. Measured diameters (D) of parent and branch vessels corresponded well to the theoretical formula: (DParent)3 = (DBranch1)3 + (DBranch2)3....,in angiographically normal coronary arteries. The exponent, on the average, is less with increasing grades of vascular disease for left main coronary artery branch-points. Mean area ratio, the sum of the cross-sectional area of the branches divided by the area of parent vessel, decreased with greater arteriographic disease. Area ratio varies with changes in the relative calibers of branch vessels. Fifty-seven branch-angles were determined by graphic analysis of postmortem biplane coronary arteriograms. No relationship could be found between branch-angle and vessel caliber. The included angle between branches varied from 32 degrees to 124 degrees without respect to relative or absolute vessel calibers. The results of these postmortem measurements on human coronary arteriogram suggest that coronary artery caliber may adjust to minimize energy loss at the branch-point but that branch-angle is determined by other factors. Restudy of arteriograms suggests that branch-angle may be determined by branch vessel destination.
The natriuretic and hypotensive effects of potassium.
Authors: Young D B , McCaa R E , Pan Y J , Guyton A C
Published: June 2012

The chronic effects of potassium loading on sodium balance and related variables were studied in two groups of dogs. The first group was intact except for the presence of indwelling arterial and venous cannulas. On the 1st day, increasing daily potassium intake from a normal level (30 mEq/day) to 200 mEq/day produced a 0.47-mEq increase in plasma potassium with a 56% increase (P greater than 0.01) in sodium excretion in spite of a 58% increase in plasma aldosterone concentration. After 6 days of potassium loading the cumulative negative sodium balance averaged 44 mEq while 22Na space decreased 6.7% (P less than 0.025). In this group arterial pressure did not change measurably. The same experimental protocol was repeated in a second group of dogs that were chronically adrenalectomized and maintained on fixed levels of aldosterone (50 mug/day) and hydrocortisone (1 mg/day). With aldosterone levels held constant the same increase in potassium intake produced a 1st day increase in potassium concentration of 1.20 mEq/liter and 217% (P less than 0.001) increase in sodium excretion. After 5 days of high potassium intake, the cumulative negative sodium balance totaled 84 mEq. Sodium space decreased 7.5% (P less than .005) during the course of the 5-day high potassium intake period. Potassium loading caused a fall in mean arterial pressure in this group; pressure fell from the control level of 110 +/- mm Hg to 87 +/- 4 mm Hg (P less than .001) after 3 days of high intake. By the 5th day of the experiment, pressure stabilized at 96 +/- 3 mm Hg, 13% less than (P less than 0.01) the control level. The results suggest that changes in plasma potassium concentration within physiological limits may have long term effects on sodium balance.
Response of aldosterone and blood pressure to angiotensin II infusion in anephric man. Effect of sodium deprivation.
Authors: Deheneffe J , Cuesta V , Briggs J D , Brown J J , Fraser R , Lever A F , Morton J J , Robertson I S , Tree M
Published: June 2012

Angiotensin II, infused intravenously, increased plasma aldosterone concentration in two of six anephric subjects taking their usual dietary quantities of sodium. After 3 days of dietary sodium restriction and weight-reducing hemodialysis, the aldosterone response to infused angiotensin II in the two previously reactive subjects was enhanced, while the four previously unreactive subjects also showed a rise in plasma aldosterone. Before and after sodium depletion the anephric subjects were less responsive than normal subjects. Even when sodium-depleted, the anephrics showed no further rise in plasma aldosterone when arterial plasma angiotensin II was increased by infusion to concentrations greater than 50-199pg/ml, in contrast to sodium-depleted normals who show progressive aldosterone responses with plasma angiotensin II concentrations up to at least 370pg/ml. Before the infusion of angiotensin II, arterial plasma renin, angiotensin II, and aldosterone were detectable in the anephrics, but were unchanged by dietary sodium restriction or weight-reducting hemodialysis. Sodium depletion caused significant falls in weight, plasma sodium, and blood pressure, but no changes in plasma potassium or cortisol. Increases in blood pressure in relation to increments of arterial plasma angiotensin II were unaffected by sodium depletion, as might be expected in the absence of a rise in endogenous angiotensin II.
Regional refractoriness within the ventricular conduction system. An evaluation of the "gate" hypothesis.
Authors: Lazzara R , El-Sherif N , Befeler B , Scherlag B J
Published: June 2012

We studied the refractoriness of Purkinje fibers with the intent of localizing critical sites of block of premature impulses. To preserve the ventricular conducting system (VCS) nearly intact in vitro, we used a modification of the Elizari preparation. This was superfused with a physiologic salt solution. Action potential durations increased progressively from the His bundle to the distal Purkinje fibers along three pathways: (1) the main right bundle branch and moderator band; (2) the anterior border fibers of the left bundle and anterior false tendons; (3) the posterior border fibers of the left bundle and posterior false tendons. The action potential durations near the terminations of the false tendons were the longest ones found. The interior fibers of the left bundle branch had action potentials of shorter duration and greater variability than those of simultaneously activated fibers in the right bundle branch or the border fibers of the left bundle branch. Similarly, on the right side, the septal branches of the right bundle had action potentials of shorter duration than those of the moderator band. We also found that the fibers with short action potential durations provided the quickest pathways to septal myocardium. When extrastimuli were applied to the His bundle, block in a bundle branch always occurred in the proximal 1 or 2 cm of the main bundle branch. Experiments performed in vivo in which extrastimuli were delivered to the atrium or His bundle and recordings made from the terminations of false tendons and the distal ends of the main right bundle branch confirmed the finding that the critical sites of block were located in the proximal main bundle branches.
The three-dimensional dynamic geometry of the left ventricle in the conscious dog.
Authors: Rankin J S , McHale P A , Arentzen C E , Ling D , Greenfield J C , Anderson R W
Published: June 2012

The dynamic geometry of the left ventricle was assessed with the use of chronically implanted pulse-transit ultrasonic dimension transducers. The orientation of the transducers allowed the measurement of left ventricular minor and major axis diameters and equatorial wall thickness in the conscious dog. The left ventricle was modeled as a three-dimensional, prolate ellipsoidal shell. Left ventricular and pleural pressures were measured with high fidelity micromanometers. Aortic blood flow was obtained with electromagnetic flow probes. To test the assumptions inherent in this technique, left ventricular mass, internal volume, stroke volume, and peak aortic flow were computed from the dimension data and compared to directly measured values. Correlation coefficients of 0.95 or greater were obtained for each of these comparisons. In addition, the calculated left ventricular mass was constant to within +/- 6% of the mean value throughout the cardiac cycle. We found that the dynamic contraction pattern of the left ventricle was dependent on the physiological state of the dog. Furthermore, in the conscious state, shortening of the minor axis diameter, lengthening of the major axis diameter, and slight thickening or thinning of the wall were noted during isovolumic contraction (isovolumic ellipticalization pattern). In the open-chested, anesthetized state, however, marked rearrangements in geometry were observed during isovolumic contraction manifested by lengthening of the minor axis diameter, and significant thickening of the wall (isovolumic sphericalization pattern). We also observed that left ventricular volume was significantly diminished in the open-chested state. The isovolumic contraction pattern in open-chested dogs could be changed from sphericalization to ellipticalization by increasing end-diastolic volume with the infusion of saline. During a vena caval occlusion in the conscious state, the contraction pattern changed from isovolumic ellipticalization to isovolumic sphericalization as the end-diastolic volume decreased. Thus, the exact pattern of left ventricular contraction was found to be a function of left ventricular volume.
A comparison of aortic baroreceptor discharge in normotensive and spontaneously hypertensive rats.
Authors: Brown A M , Saum W R , Tuley F H
Published: June 2012

Electrophysiological characteristics of individual aortic baroreceptors from normotensive rats (NTR) and spontaneously hypertensive rats (SHR) were compared. Impulse activity of afferent fibers was examined following the application of pressure steps to an in vitro aortic arch-aortic nerve preparation. Thirty-one fibers including seven unmyelinated fibers were studied completely over the range of 0-260 mm Hg, using steps 1-30 seconds in duration. The pressure threshold for peak transient discharge of baroreceptors of SHR's was 88.4 +/- 10.1 (mean +/- SE) mm Hg, whereas for baroreceptors of NTR's it was 77.5 +/- 9.3 mm Hg. The pressure threshold for steady state discharge was 137.3 +/- 5.2 mm Hg for SHR baroreceptors and 103.5 +/- 7.1 for NTR baroreceptors. These values compare favorably to measurements in vivo in the rat. The relationship between peak transient impulse frequency and pressure was linear, whereas the relationship between steady state impulse frequency and pressure was hyperbolic. The curvature of the steady state frequency-pressure curves was significantly reduced for baroreceptors of SHR's. The steady state pressure-volume curves of the aortas of SHR's and NTR's were similar, so that a reduction in distensibility could not account for the larger, significant differences in threshhold and sensitivity. Therefore resetting cannot be attributed simply to reduced vascular compliance.
Bioassay in vivo for circulating vasoactive agents after renal artery constriction in dogs.
Authors: Pamnani M B , Simon G , Overbeck H W
Published: June 2012

We used the gracilis muscle vascular bed to bioassay blood from the two renal veins, vena cava, and aorta continuously for the presence of vasoactive agents before and for 45 minutes after partial occlusion of the left renal artery in dogs. Compared to comparable blood samples from control dogs, left renal venous, vena caval, and aortic blood, but not right renal venous blood, from dogs with renal artery constriction developed vasoconstrictor activity. This was associated with increased renin concentration in plasma from the left renal vein and the vena cava and an increase in systemic arterial pressure. In dogs pretreated with indomethacin, blood from the right renal vein also showed vasoconstrictor activity. Pretreatment with antirenin serum abolished all of the differences between control and experimental dogs. These findings suggest that during acute unilateral renal artery constriction the constricted kidney releases renin and the contralateral kidney releases prostaglandins in sufficient quantity to produce systemic vascular effects.
The response of canine coronary vascular resistance to local alterations in coronary arterial P CO2.
Authors: Case R B , Greenberg H
Published: June 2012

The effect of hypercapnia on coronary vascular resistance (CVR) was studied in seven open-chest dogs. Coronary blood flow was supplied to the cannulated left main coronary artery from the femoral artery by a precision pump. Coronary arterial PCO2 was locally controlled with a small membrane oxygenator in the coronary perfusion circuit. Each PCO2 change was made at a constant coronary flow, and CVR was calculated from the ratio of perfusion pressure to flow. Coronary sinus (CS) PCO2 and PO2 were recorded continuously from blood withdrawn through a CS catheter. Normocapnia (PCO2 = 42.3 +/- 2.8 mm Hg) was obtained with a membrane oxygenator gas composition of 95% O2-5% CO2, and hypocapnia was produced with 100% O2-0% CO2. In addition to physiology normal coronary flow (determined by a CS PO2 of 20-30 mm Hg) relatively high and low flow states were studied. At a normal control CS PO2, a decrease in coronary arterial PCO2 from 42.3 +/- 2.8 to 23.8 +/- 1.3 mm Hg caused CVR to increase by 84.2%, from 1.27 +/- 0.06 to 2.30 +/- 0.04 units. Since pH was inversely related to PCO2, the effect on CVR may have been mediated through a pH change. CS PCO2 decreased from 65.2 +/- 1.9 to 39.4 +/- 1.3 mm Hg. myocardial oxygen consumption was unchanged. Increases in CVR of 74.5, 119.5, and 69.3% occurred during hypocapnia in three additional experiments in which control arterial PO2 was maintained at 52-90 mm Hg. When CS PO2 was greater than 30 mm Hg, the normocapnic CVR was high, and was only minimally increased by hypocapnia. When coronary flow was reduced to an ischemic level there was little response in CVR to hypocapnia. Thus the level of arterial PCO2 can have an important effect on CVR independent of changes in O2 consumption. Myocardial PCO2, derived from metabolically produced CO2 and contributed to by arterial CO2, may be a major factor in normal control of coronary flow.
Inhibition of adrenergic neurotransmission in canine vascular smooth muscle by histamine: mediation by H2-receptors.
Authors: McGrath M A , Shepherd J T
Published: June 2012

Histamine depressed the contractions of dog saphenous vein strips caused by stimulation of their sympathetic nerves. This was due to a decrease in the release of norepinephrine which appears to be mediated by histamine H2-receptors. The evidence for this is as follows: (1) Contractions of the strips caused by activating the nerve endings electrically or by depolarization with potassium ions were depressed by histamine, whereas contractions caused by tyramine and norepinephrine were either unchanged or augmented. (2) Strips were incubated with norepinephrine[7-3H] and mounted for superfusion and isometric tension recording. The perfusate was collected for estimation of total radioactivity and for column chromatographic separation of norpinephrine and its metabolites. Histamine (0.9 muM) depressed the release of norepinphrine[7-3H] during contractions caused by electric stimulation, whereas the release of radioactive compounds caused by tyramine was unaffected. (3) The depression by histamine of the contractions and the efflux of radioactive compounds caused by electric stimulation were inhibited by an H2-receptor antagonist (metiamide), but were unaffected by an H1-receptor antagonist (pyrilamine). (4) Contractions caused by electric stimulation were inhibited by an H2-receptor agonist (4-methylhistamine) and augmented by an H1-receptor agonist (2-methylhistamine). These findings suggest the possibility that histamine, which is abundant in sympathetic nerves, might have a regulatory role in the release of the neurotransmitter.
Effects of sodium nitroprusside and nitroglycerin on tension prolongation of cat papillary muscle during recovery from hypoxia.
Authors: Brodie B R , Cuck L , Klausner S , Grossman W , Parmley W
Published: June 2012

Because of recent studies suggesting that vasodilators affect ventricular compliance, we studied the effect of sodium nitroprusside and nitroglycerin on the mechanical performance of 21 isolated cat papillary muscles. The muscles were stimulated isometrically at 36 beats/min. Sixteen of the muscles were made hypoxic (95% N2, 5% CO2) for 50 minutes and then reoxygenated. Sodium nitroprusside (10(-5) M) added to four of these muscles prior to hypoxia substantially diminished the tension prolongation (both the time to peak tension, TTP, and time for tension to fall to 1/2 its peak value, RT 1/2) that characterizes recovery from hypoxia. TTP and RT 1/2 measured 2 minutes after reoxygenation were 300 +/- 20 msec and 528 +/- 26 msec for the control muscles compared to 208 +/- 13 msec and 248 +/- 22 msec for the muscles pretreated with nitroprusside. Nitroprusside had no effect on the fall and recovery of peak developed force or on the rise and fall of resting force. Furthermore, nitroprusside had no effect on the above parameters in nonhypoxic muscles. We also found that nitroprusside in concentrations of 10(-7) M and nitroglycerin in concentrations of 10(-5) M had little or no effect on tension prolongation. The results of the study indicate that nitroprusside is capable of blocking the tension prolongation that occurs during recovery from hypoxia and may prevent the incomplete myocardial relaxation thought to characterize this phenomenon. Since nitroglycerin had no effect on tension prolongation, it is possible that other factors also may be important in the apparent increase in left ventricular compliance associated with administration of vasodilators to patients.
The role of arterial baroreceptors in the regulation of arterial pressure in conscious dogs.
Authors: McRitchie R J , Vatner S F , Heyndrickx G R , Braunwald E
Published: June 2012

To elucidate the role of arterial baroreceptors in the acute regulation of arterial pressure in the conscious animal, arterial pressure was lowered and raised in intact, conscious dogs, and in dogs after bilateral section of both carotid sinus and aortic nerves (total arterial baroreceptor denervation, TABD). Pressure was altered by intravenous bolus injections and continuous infusions of nitroglycerin and methoxamine and also by hemorrhage. TABD resulted in a change in peak mean arterial pressure 2-4 times as great as that seen in intact dogs following injection of nitroglycerin or methoxamine. However, when the time taken for the arterial pressure disturbance to return to control levels, as well as the absolute change in arterial pressure, was considered (the pressure-time product), responses of dogs with TABD were far greater for nitroglycerin (7-9 times that seen in intact dogs) and methoxamine (11-15 times). Arterial pressure responses of dogs with selective section of the carotid sinus nerves were intermediate but closer to those of intact dogs than to dogs with TABD. With infusion of drugs or following hemorrhage, responses of mean arterial pressure were 3- to 5-fold greater in dogs with TABD than in intact dogs, indicating that the static open loop gain of the arterial baroreceptor system ranged from 2 to 4.
A delayed suppression of the renin-aldosterone axis following saline infusion in human hypertension.
Authors: Tuck M L , Williams G H , Dluhy R G , Greenfield M , Moore T J
Published: June 2012

The purpose of this study was to compare the acute suppressibility of the renin-angiotensin-aldosterone (RAA) axis in normotensive (n = 23) and essential hypertensive (n = 62) subjects. Only those hypertensive subjects with normal plasma renin activity (PRA) levels (sodium restricted, upright) were included in the study. Acute suppression of the RAA axis was determined by measuring PRA, plasma angiotensin II (A II), and plasma aldosterone (PA) at frequent intervals during the infusion of isotonic saline (500 ml/hour for 6 hours). Although all parameters fell significantly from control levels by 20-30 minutes in the normotensive subjects, we found that 60% of the hypertensive subjects showed no significant decline in PRA or PA until 120-240 minutes after beginning the infusion. The other hypertensive subjects showed normal RAA suppression. In addition, while there were no significant differences between the three groups in control PRA or PA levels, we found that the PA levels from 30 to 240 minutes during the saline were significantly higher (P less than 0.01) in the hypertensive subjects with delayed suppression. That there were two distinct populations in the hypertensive group was suggested by the bimodality of the frequency response curve, with peaks occurring at 30 and 240 minutes. These studies indicate an abnormality in the acute suppression of the RAA axis in a substantial proportion of subjects with normal renin essential hypertension. Since previous studies in normal subjects have reported that the early phase of response to saline infusion is related to the sodium ion per se and not to intravascular volume expansion, we have come to the conclusion that the present data are consistent with the hypothesis that the delayed suppression hypertensive group has a diminished ability to respond to the sodium ion.
Inhibition of feline collateral vessel development following experimental thrombolic occlusion.
Authors: Schaub R G , Meyers K M , Sande R D , Hamilton G
Published: June 2012

We compared development of feline hindlimb collateral circulation after acute occlusion of the terminal aorta by ligation, thrombus formation, and formation of a "closed" aortic loop containing thromboplastin. Collateral circulation development was assessed by aortograms, scintillation scans, neurological signs following occlusion, measurement of hindlimb muscle blood flow, and forelimb and hindlimb temperature. In cats in which aortic occlusion was the result of ligation or thromboplastin in the aortic loop, paralysis was not evident. Aortograms and scintillation scans indicated hindlimb blood flow. Both muscle temperature and blood flow data indicated that the return of blood flow was rapid. The 5th lumbar artery appears to be the origin of the collateral vessels. The mid-zone component is a dorsal and ventral vertebral route and an epaxial muscle route. The reentry components are the 6th or 7th lumbar arteries. The collateral vessels arise from preexisting collateral vessels. Of those cats in which aortic occlusion was the result of a thrombus, all exhibited paralysis. Aortograms, scintillation scans, muscle temperature, and hindlimb blood flow data indicated reduced hindlimb blood flow. The results suggest that the thrombus has an inhibitory effect on the development of collateral circulation.