bluuebunny/crossref_metadata_2025 huggingface dataset:
Studies on the mechanism of pulmonary vascular responses to miliary pulmonary embolism.
Authors: Kealey G P , Brody M J
Published: June 2012

The nature and mechanisms of pulmonary vascular responses which follow miliary pulmonary embolism were examined in intact dogs in which the isolated left lower lobe was perfused at constant blood flow. Embolization of the lung with plastic microspheres increased total pulmonary vascular resistance, whereas, in contrast, vascular resistance of the isolated perfused left lower lobe which was protected from embolization was decreased. This vasodilation was prevented by chronic denervation of the lobe and by ganglionic blockade. Cervical vagotomy also blocked the response but atropine failed to alter the vasodilation. The response, which appeared to be reflex in origin and involve efferent sympathetic pathways, was prevented by beta-adrenergic receptor blockade produced by propranolol. Since the lobar vascular response to norepinephrine was significantly enhanced by propranolol, it was concluded that embolization of the lung evokes pulmonary vascular reflex vasodilation which is mediated over the sympathetic nervous system via a beta-adrenergic receptor mechanism.
The effects of ouabain on the transmembrane potentials and intracellular potassium activity of canine cardiac Purkinje fibers.
Authors: Miura D S , Rosen M R
Published: June 2012

Open-tip microelectrodes containing a potassium-sensitive liquid ion exchanger (Corning 477317) were used to study the effects of ouabain on the intracellular potassium activity and the transmembrane potentials of beating canine cardiac Purkinje fibers. The preparations were superfused with Tyrode's solution containing ouabain, 2 X 10(-7) M, and potassium, 4 mM, for 30 minutes. At the end of this period, intracellular potassium activity had decreased from the control value of 130.0 mM to 112.2 mM. The resting membrane potential determined through conventional 3 M KC1-filed microelectrodes decreased from -83.6 to -78.8 mV. Comparison of the decrease in the potassium equilibrium potential with the decrease in the resting membrane potential suggests that there was an accumulation of potassium at the exterior surface of the cell membrane. The effect of ouabain on the resting membrane potential, therefore, was due to a change in the transmembrane potassium ion gradient. This, in turn, resulted from a decrease in intracellular potassium activity and, apparently, from an increased potassium activity at the cell surface.
Assessment of regional myocardial blood flow and regional fractional oxygen extraction in dogs, using 15O-water and 15O-hemoglobin.
Authors: Parker J A , Beller G A , Hoop B , Holman B L , Smith T W
Published: June 2012

A new approach to the assessment of regional myocardial blood flow and fractional oxygen extraction has been developed using 15O-water (H2-15O) and 15O-hemoglobin (15O-Hb). Bolus doses (1 mCi) of H2-15O and 15O-Hb were injected 10 minutes apart into the left main coronary artery of 12 normal dogs. Sequential images of regional myocardial tracer clearance were obtained over 5 minutes with a positron camera. Myocardial blood flow calculated from the monoexponential washout of H2-15O after background correction was 78 +/- 6 (SE) ml/100 g per min. Functional images of regional blood flow in which the image of peak activity was divided by the integrated image of H2-15O washout were derived by computer processing. These images demonstrated homogeneous blood flow in the normal myocardium. Fractional myocardial O2 extraction was determined from an image of initial distribution of O2 used (obtained by extrapolating back to time zero the series of images obtained after 15O-Hb administration), divided by initial distribution of O2 delivered (obtained by back extrapolating H2-15O washout). These functional images showed uniform distribution of fractional O2 extraction in the normal myocardium. Thus, these studies show that regional myocardial blood flow and regional oxygen extraction can be measured simultaneously by sequential imaging after serial intracoronary injections of H2-15O and 15O-Hb.
The influence of the pituitary on arterial intimal proliferation in the rat.
Authors: Tiell M L , Stemerman M B , Spaet T H
Published: June 2012

The formation of arteriosclerotic fibromusculoelastic intimal thickening following arterial de-endothelialization is well documented. Recent findings, both in vitro and in vivo, suggest that platelets are a major participant in the pathogenesis of this lesion by releasing a mitogen to medial smooth muscle cells (SMC). This mitogen results in SMC migration to and proliferation within the intima. A similar mitogen has been described as originating in brain and pituitary tissue. We now report that, in hypophysectomized rats with normal platelet counts, intimal hyperplasia is markedly delayed; pair-fed intact controls normally develop lesions. It therefore appears that the pituitary gland plays a significant role in the experimental arteriosclerotic response.
Suppression of calcific fibrous-fatty plaque formation in rabbits by agents not affecting elevated serum cholesterol levels. The effect of thiophene compounds.
Authors: Chan C T , Wells H , Kramsch D M
Published: June 2012

We tested the suppressive effect of antihypercalcemic-hyperphosphatemic agents on atherogenesis. We studied five groups of rabbits for 8 weeks, one control group and four groups on a fibrogenic atherogenic diet. One group received the atherogenic diet alone, and the remaining three atherogenic groups were treated simultaneously with 2-thiophenecarboxylic acid (ThCA), 5-methyl-2-thiophenecarboxylic acid (5-CH3-ThCA), and 5-bromo-2-thiophenecarboxaldehyde (5-Br-ThCA). Rabbits receiving the atherogenic diet alone developed: (1) elevations of serum cholesterol, calcium, and phosphorus; (2) massive fibrous-fatty aortic plaques with excessive accumulation of aortic collagen, elastin, and lipids; (3) marked deposition of calcium and phosphorus in both aortic tissue and elastin; and (4) severe lipid infiltration of the liver. Treatment with all three drugs normalized the elevated serum calcium but not the cholesterol levels, and effectively inhibited all aspects of the atherosclerotic process as determined morphologically and biochemically. The order of effectiveness was: 5-CH3-ThCa greater than 5-Br-ThCA greater than ThCA. No bone resorption occurred in the treated groups. The normalizing effects of the thiophene compounds on serum phosphorus levels were not significant at the dosages used.
Effect of l-dopa on sympathetic nerve activity and blood pressure in the spontaneously hypertensive rat.
Authors: Judy W V , Watanabe A M , Henry D P , Besch H R , Aprison B
Published: June 2012

We examined the effect of L-Dopa, after peripheral L-amino acid decarboxylase inhibition, on sympathetic nerve activity (SNA) and blood pressure in spontaneously hypertensive rats (SHR) and in normotensive control rats. L-Dopa reduced SNA in both groups of animals. The SHRs were significantly more sensitive to the depressor effect of L-dopa than were the control animals, the threshold dose for reduction of SNA being 3 mg/kg in the SHR and 15 mg/kg in control rats. Similarly, the magnitude of inhibition of SNA was substantially greater in the SHR than in normotensive rats. The reduction in SNA in the SHR accompanied by a parallel fall in blood pressure. In contrast, blood pressure in control rats did not change significantly, even though SNA was diminished. Studies of the penetration of L-dopa into the cerebral parenchyma revealed that equivalent amounts of the amino acid entered the brains of the two groups of rats. These results suggest that the SHRs are more sensitive to the SNA-inhibiting effects of L-dopa than are normotensive rats. In addition, they confirm our previous suggestion that excessive SNA plays a causative role in the hypertension of the SHR.
The effects of acetylcholine on the electrical activity of canine cardiac Purkinje fibers.
Authors: Gadsby D C , Wit A L , Cranefield P F
Published: June 2012

We studied the effects of acetylcholine (ACh) on small bundles of canine cardiac Purkinje fibers exposed to normal, or low-chloride (isethionate) Tyrode's solution in a rapid superfusion system. In superfusate containing 4 mM K+, the resting potential of Purkinje fibers may be either "low," near -40 mV, or "high," near -90 mV. ACh, at 10(-6) to 10 (-5) M, increased the membrane potential from both the low and high resting levels and, in low-Cl solution, often induced a maintained shift in potential from the low to the high level. The increase in membrane potential caused by ACh was greater at the low than at the high level. ACh, at 10(-6) to 10(-5) M, reduced action potential duration in both normal and low-Cl Tyrode's solution, the effect being more marked in the latter. These effects of ACh were reversibly abolished by atropine (5 X 10(-5) M), indicating that they were mediated via muscarinic ACh receptors, and they probably result from an increase in membrane K+ conductance since 10(-5) M ACh reversibly reduced, by 13% on the average, the amplitudes of the steady changes in membrane potential evoked by applying small current pulses (-5 to -25 nA, 200 msec). ACh (10(-5) M) also diminished the rate of, or stopped, spontaneous activity arising from either level of membrane potential. The cessation of spontaneous slow response activity, arising from the low level, sometimes was accompanied by a maintained shift of the membrane potential to the high resting level. It is concluded that the action of ACh on Purkinje fibers is qualitatively similar to its action on sinoatrial nodal and atrial cells.
Aortic pulse wave velocity, elasticity, and composition in a nonhuman primate model of atherosclerosis.
Authors: Farrar D J , Green H D , Bond M G , Wagner W D , Gobbeé R A
Published: June 2012

Aortic pulse wave velocity was determined in Macaca fascicularis monkeys fed either atherogenic or control diets for 36 months. The foot-to-foot velocity and apparent phase velocities of the second through seventh Fourier harmonics at a given diastolic pressure in the atherosclerotic monkeys were 1.5 to 2.0 times the values for the control animals. More than 80% of the aortic intimal surface of the atherosclerotic monkeys was covered with fibrous or fatty plaque, which approximately doubled wall thickness and wall thickness to radius ratio. Angiochemical evaluations showed no difference in collagen or elastin concentration (as a fraction of lipid and mineral-free dried aorta), but the atherosclerotic aortas were 1.5 to 2.0 times that of control in collagen and elastin content (defined as the absolute quantity beneath a square centimeter of intimal surface). Total cholesterol and calcium concentrations in the atherosclerotic aortas were more than 10 times the values for the control aortas. The static circumferential distensibility of the excised atherosclerotic aortas was significantly less than control, but there was no difference in incremental (Young's) modulus of elasticity. The in vitro pressure-strain elastic modulus of the atherosclerotic aortas was more than twice that of control, which was predicted from the enhanced wave velocity. The significantly increased stiffness of the atherosclerotic arteries appeared to be due mainly to the increased wall thickness caused by the atherosclerotic plaques rather than to material changes described by Young's modulus. Extensive medial damage, however, also was present and could have had a major influence on stiffness. Atherosclerosis therefore can result in increased aortic stiffening, detectable by pulse wave velocity, even if there is no change in the overall Young's modulus of elasticity.
Diet and sire effects on serum cholesterol and cholesterol absorption in infant baboons (Papio cynocephalus).
Authors: Mott G E , McMahan C A , McGill H C
Published: June 2012

One hundred three baboon infants, the progeny of an equal number of dams and seven sires, were breast fed or were fed prepared formulas containing 1.2, 29, or 61 mg/dl cholesterol for 14 weeks. We measured serum cholesterol and triglyceride concentrations at birth and at 3-week intervals, and cholesterol absorption at 12 weeks. Dietary cholesterol had a significant effect on serum cholesterol concentration at 12 weeks and on cholesterol absorption, but did not affect weight or serum triglyceride concentration. Sire had a significant effect on serum cholesterol concentration at birth and at 12 weeks, but the effect at birth did not predict the effect at 12 weeks. Sire did not affect cholesterol absorption, serum triglyceride concentration, or weight at 12 weeks. The sire effect on serum cholesterol concentration in infancy is not mediated by control of cholesterol absorption. Males weighed more than females at 12 weeks, but sex did not affect serum cholesterol concentration, triglyceride concentration, or cholesterol absorption.
The effects of intra-arterial and intraportal injections of vasopressin on the simultaneously perfused hepatic arterial and portal venous vascular beds of the dog.
Authors: Richardson P D , Withrington P G
Published: June 2012

The hepatic arterial and hepatic portal venous vascular beds of the chloralose-urethane anesthetized dog were perfused simultaneously in situ. Vasopressin (10 mU = 1 unit) was injected in graded increasing doses into the hepatic artery and into the portal vein. Both intra-arterial and intraportal vasopressin elicited both hepatic arterial vasoconstriction and hepatic venous dilation; the delay in onset of both hepatic vascular effects was significantly shorter than that for any succeeding systemic effects (a rise in systemic arterial pressure and fall in heart rate), showing that they were not attributable to recirculation or to arterial baroreceptor reflexes. Injections of vasopressin into the inferior vena cava at the level of the hepatic veins consistently produced smaller hepatic vascular effects than either intra-arterial or intraportal injections of the same doses. The results are discussed in the context of the therapeutic role of vasopressin in controlling gastrointestinal bleeding and portal hypertension.
Renal chemoreceptors in the rat.
Authors: Recordati G M , Moss N G , Waselkov L
Published: June 2012

There are afferent nerve fibers responsive to alterations of the kidney's chemical environment in the renal nerves of the rat. In anesthetized, artificially ventilated, male Sprague-Dawley rats, single unit recordings were prepared by dissection of the centrally cut nerves of the right kidney. The stimuli used included occlusion of the renal artery, systemic asphyxia, changes in renal arterial and venous pressures, changes in ureteral pressure, and cyanide infusion. We found a population of sensory nerve fibers whose endings are activated only during markedly impaired renal blood flow (produced by clamping the renal artery, severe hypotension below 40 mm Hg, and prolonged occlusion of the renal vein), and during systemic asphyxia. The same units are not responsive to increases and decreases in systemic arterial pressure (range: 40--190 mm Hg), to ureteral pressure (range: 0--50 mm Hg), or to changes in renal venous pressure. None of the 40 single units studied was spontaneously active; their pattern of activation during renal ischemia always was characterized by trains of impulses. These sensory units have functional properties distinctly different from those of known renal mechanoreceptors. They appear to be a homogeneous group of sensory elements, and we have termed them renal ("R") chemoreceptors. Evidence also is presented which is consistent with the concept that a chemical substance released by or accumulated within the kidney might be the agent activating these chemoreceptors during renal ischemia.
Increased renal vascular reactivity to angiotensin II but not to nerve stimulation or exogenous norepinephrine in renal hypertensive rats.
Authors: Collis M G , Vanhoutte P M
Published: June 2012

We isolated and perfused both the "clipped" and "contralateral" kidneys from Goldblatt renal hypertensive and sham-operated control rats, 1--104 days postoperatively. Responses to renal nerve stimulation were depressed in clipped kidneys from hypertensive rats (1 day postoperative), and these kidneys were supersensitive to exogenous norepinephrine (1--31 day) when compared with the contralateral organ of the same animal. Similar alterations were found between clipped and contralateral kidneys from sham-operated control rats. There was no difference in responses to renal nerve stimulation of norepinephrine between clipped kidneys from hypertensive and control rats, but clipped kidneys from hypertensive rats were supersensitive to angiotensin II (17 and 31 days). Comparison of contralateral kidneys from hypertensive and control rats revealed no change in norepinephrine sensitivity or in responses to renal nerve stimulation, but there was a reduction in the slope of the dose-response curve to norepinephrine and of the maximal effect of the catecholamine (104 days) and a pronounced supersensitivity to angiotensin II (17--104 days) in the hypertensive rats. These results indicate that (1) renal nerve function and norepinephrine sensitivity of the isolated renal vasculature are unchanged in renal hypertension, but clipping partially denervates the kidney causing depressed nerve function and unilateral norepinephrine supersensitivity, unrelated to hypertension; (2) the prolonged high pressure load on the contralateral kidney may impair the function of the vascular smooth muscle; and (3) bilateral supersensitivity to angiotensin II is associated with hypertension but is not solely a consequence of the high pressure.
Antagonistic effects of theophylline and adenosine on adrenergic neuroeffector transmission in the rabbit kidney.
Authors: Hedqvist P , Fredholm B B , Olundh S
Published: June 2012

The actions of adenosine and theophylline on adrenergic neuroeffector transmission were studied in the rabbit kidney perfused with Tyrode's solution in which the norepinephrine stores had been labeled with (-)-norepinephrine[3H] ((-)-NE[3H]). We found that adenosine inhibited (-)-NE[3H] release induced by nerve stimulation, increased basal perfusion pressure, and enhanced the vasoconstrictor response to nerve stimulation and norepinephrine in a dose-dependent manner. Theophylline per se had effects on neuroeffector transmission opposite to those of adenosine. All effects of adenosine were antagonized effectively or annulled by theophylline in concentrations having little or no effect on rabbit kidney phosphodiesterase activities. Two other compounds, Ro 20-1724 and ZK 62.711, being equally potent or more potent than theophylline as phosphodiesterase inhibitors, failed to antagonize adenosine-mediated inhibition of (-)-NE[3H] release by nerve stimulation. Ro 20-1724 in high concentration (10(-4) M) inhibited the vasoconstrictor response to nerve stimulation, but it had little additional effect on the enhancement by adenosine. These findings suggest that theophylline specifically antagonizes the effects of adenosine on pre- and postjunctional transmission in the kidney. The results also are consistent with the view that endogenous adenosine may play a role as modulator of adrenergic neuroeffector transmission.
Sinus node response to premature atrial stimulation in the rabbit studied with multiple microelectrode impalements.
Authors: Steinbeck G , Allessie M A , Bonke F I , Lammers W J
Published: June 2012

In this study we investigated the response of the isolated rabbit sinus node to ectopic atrial premature beats elicited late in the atrial cycle. In three experiments the response of at least 45 different fibers of the sinus node was recorded, whereas, in other experiments, investigation was less extensive. In this way the spread of activation of the total pacemaker area could be mapped accurately both during spontaneous beating and the induction of ectopic atrial beats of different degrees of prematurity. We found that: (1) The conduction of an impulse from the dominant pacemaker area to the atrium during spontaneous rhythm (antegrade conduction) is slower than the conduction of an ectopic atrial impulse towards the center of the sinus node (retrograde conduction). (2) The action potential of the dominant pacemaker fibers in the sinus node is shortened because of premature activation caused by an ectopic impulse from the atrium. Late premature beats had no effect on diastolic depolarization. If the retrograde activation wave did not reach the area of the dominant pacemaker before the spontaneous discharge of these fibers, there was electrotonic influence demonstrable over a distance of about 0.5 mm. (3) Comparison of the true sinoatrial conduction time with the estimated sinoatrial conduction calculated indirectly from the length of the postextrasystolic atrial cycle revealed that, in the isolated rabbit heart, the calculated value is a serious underestimation of the true antegrade sinoatrial conduction time.
Chemical characteristics of a high molecular weight renin from the renal cortex of the dog.
Authors: Potter D M , McDonald W J , Dunn P M , Metcalfe J
Published: June 2012

We found an acid extract of normal dog kidneys to contain two distinct molecular weight forms of renin-like activity. Gel filtration chromatography showed peaks of activity as estimated molecular weights of 65,000 and 41,000. The high molecular weight fraction (HMW) comprised only 1% of the total activity of the extract. Both HMW and low molecular weight (LMW) fractions were inhibited by anti-human renin antibody and had similar broad pH-dependent activity optima between pH 6.0 and 7.5 in homologous substrate. The Michaelis constant (Km) of HMW was 3.6 times the Km of LMW. Both renins bound reversibly to concanavalin A-Sepharose with comparable affinities. HMW and LMW eluted from DEAE-Sephadex at similar salt concentrations without conversion of HMW to LMW. Transient acidification effected partial conversion of HMW to LMW without changing the total activity. Preincubation of HMW with trypsin increased the activity 40% and effected complete conversion of HMW to LMW. The apparent molecular weight difference between HMW and LMW is probably due to a covalently bound fragment(s) and not to a noncovalently bound moiety such as has been described in the rabbit and the hog. Both HMW and LMW are glycoproteins whose terminal sugar constituents possibly are similar. HMW dog renin is a new molecular form of renin that is convertible to a more active lower molecular weight renin with tryptic proteolysis.
The circulatory influences of vagal afferents at rest and during coronary occlusion in conscious dogs.
Authors: Bishop V S , Peterson D F
Published: June 2012

We studied the role of cardiopulmonary vagal afferents in the cardiovascular responses to coronary artery occlusion in conscious dogs with intact carotid sinuses and following functional denervation of the arterial baroreceptors. The contributions of vagal afferents were determined by cold blocking the vagi. In dogs with intact carotid sinuses, coronary artery occlusion produced small decreases in mean cardiac output and arterial pressure, whereas heart rate increased by 35 beats/min. In dogs with intact carotid sinuses, vagal cold block increased mean arterial pressure by 22 +/- 2 (mean +/- SE) mm Hg and heart rate by 90 +/- 6 beats/min. Mean cardiac output increased by 505 +/- 90 ml/min. With the exception of heart rate, responses to coronary occlusion during vagal cold block were similar to the occlusion response prior to vagal cold block. Furthermore, prior occlusion of the coronary artery did not significantly influence the responses to vagal cold block. After arterial baroreceptor denervation, coronary artery occlusion resulted in a substantially greater fall in systemic arterial pressure (-52 mm Hg as compared to -8 mm Hg, with intact carotid sinuses) and peripheral resistance decreased by -0.49 peripheral resistance units (PRU). Vagal cold block following denervation increased the arterial pressure by 49 +/- 10 mm Hg and peripheral resistance by 0.59 +/- 0.13 PRU. Both values were significantly greater than those observed during vagal cold block prior to denervation. In arterial baroreceptor-denervated dogs, vagal blockade significantly attenuated the response to coronary occlusion. Therefore, in conscious dogs, vagal afferents from cardiopulmonary receptors exert a significant inhibitory influence on the peripheral vascular tone. When the carotid sinuses are intact, this inhibitory influence appears to be marked during myocardial ischemia. In the absence of functional arterial baroreflexes, vagal afferent activity contributes to the depressor responses observed during ischemia.
A solid angle analysis of the epicardial ischemic TQ-ST deflection in the pig. A theoretical and experimental study.
Authors: Richeson J F , Akiyama T , Schenk E
Published: June 2012

The solid angle theory has long been applied to the interpretation of the ECG; however, quantitative evaluation of its applicability has been minimal. We applied solid angle analysis to the interpretation of the TQ-ST deflection during acute ischemia. Five anesthetized pigs were studied 1--3 hours after coronary occlusion. Multiple unipolar tracings were recorded from precisely determined positions on the epicardium overlying the ischemic and normal zones. The geometry of the hearts and ischemic zones was preserved, the margins of ischemia being defined as the outer border of Thioflavin S nonfluorescence. Wax replicas of the hearts with ischemic zones removed were constructed. Solid angles subtended at electrode positions on the replicas were calculated. A linear relationship (r = 0.84 - 0.97, P less than 0.001) was shown to exist between the observed TQ-ST deflection and the calculated solid angle. A small but patterned deviation from exact fit of the TQ-ST deflection with the calculated solid angle led us to investigate the possibility that dipole moment strength (phi) is not confined to the ischemic margins. Computations using idealized heart models with ischemic zones cylindrical and transmural in shape allowed us to distribute phi arbitrarily within the ischemic zone, comparing this predicted pattern of TQ-ST deflection with that observed experimentally. The experimental data appear most consistent with the condition in which phi is distributed over a 1-cm border region during the first several hours of ischemia. We conclude that the solid angle theory provides a rational basis for interpretation of the ischemic TQ-ST deflection; however, phi may be distributed over a marginal zone.
Modulation by prostaglandin synthesis inhibitors of the action of exogenous angiotensin II on glomerular ultrafiltration in the rat.
Authors: Baylis C , Brenner B M
Published: June 2012

We studied the effects of angiotensin II (A II) infusion, with and without inhibition of prostaglandin (PG) synthesis, on the determinants of glomerular ultrafiltration in 27 plasma volume-expanded Munich-Wistar rats. The effects of PG inhibition alone and infusion of vehicle alone also were investigated. With a pressor dose of A II single nephron (SN) GFR and total GFR did not change significantly, despite declines in both glomerular plasma flow rate (QA) and the ultrafiltration coefficient (Kf), due to an offsetting rise in the transcapillary hydraulic pressure difference (deltaP). Afferent and efferent arteriolar resistances (RA and RE) increased by approximately 100% above control during A II infusion. Inhibition of PG synthesis alone and infusion of vehicle alone similarly failed to affect SNGFR and total GFR, and only slight changes occurred in the determinants of glomerular ultrafiltration in these rats. When A II infusion was accompanied by inhibition of PG synthesis, however, profound declines in SNGFR and total GFR were seen, due to further reductions in QA and 2-fold greater increases in RA and RE than occurred with the same dose of A II alone. The A II-induced fall in Kf was not affected by simultaneous PG inhibition. Thus, endogenous PGs attenuate the vasoconstrictor actions of A II on the superficial renal microvasculature and minimize changes in QA, SNGFR, and total GFR. It is likely that an interaction between A II and PG may be important in pathophysiological conditions in which endogenous A II levels are elevated.
Segmental alpha-receptor-mediated vasoconstriction in the canine coronary circulation.
Authors: Kelley K O , Feigl E O
Published: June 2012

Recent studies from this laboratory have indicated that sympathetic alpha-receptor-mediated coronary vasoconstriction can compete with local metabolic vasodilation to reduce the oxygen supply to the myocardium. In vitro studies from other laboratories on isolated coronary vessel strips suggest that large epicardial vessels are the dominant site of adrenergic alpha-receptor activity. In this study we used anesthetized, open-chest dogs to test the hypothesis that alpha-receptor-mediated vasoconstriction occurs predominantly in epicardial vessels, which are partially removed from the metabolic milieu in the myocardium. Adrenergic beta-receptor blockade was achieved by propranolol (3 mg/kg, iv). The circumflex coronary artery was pump-perfused at constant pressure to minimize passive changes in large vessel resistance. Pressure was measured at the tip of the perfusion cannula sealed in the circumflex artery, and in an apical branch of the circumflex artery. Large vessel resistance was calculated as the pressure gradient along the vessel segment divided by the coronary flow. Intracoronary injections of nitroglycerin were used as an independent measure of the vasomotor responsiveness of the large vessel segment. Adrenergic alpha-receptor activation was produced by intracoronary bolus injections of norepinephrine and by electrical stimulation of the left stellate ganglion. Alpha-receptor stimulation caused an increase in total coronary vascular resistance; however, the relative increase in the resistance of the large vessel was only about 60% of that seen for the entire coronary bed. These data suggest that, contrary to the proposed hypothesis, adrenergic alpha-receptor-mediated vasoconstriction in the large coronary vessels is not proportionally greater than that observed in the total coronary vascular bed.
Age-related changes in Purkinje fiber action potentials of adult dogs.
Authors: Rosen M R , Reder R F , Hordof A J , Davies M , Danilo P
Published: June 2012

To determine the effects of age on electrophysiological properties of Purkinje fibers (PF), we used standard microelectrode techniques to study PF from normal beagles of five age groups: 19.1 +/- 0.8, 63.7 +/- 2.6, 88.3 +/- 1.9, 107.2 +/- 1.6, and 132.3 +/- 4.3 months (mean +/- SE). Maximum diastolic potential (MDP) did not change over this age range. Action potential (AP) amplitude and maximum upstroke velocity of phase 0 (Vmax) attained peak values at 63.7 months and then declined. As age increased there was an increase in phase 1 repolarization, a prolongation in the time to the peak of the plateau, and a decrease in plateau height. AP duration reached a maximum at 63.7 months and thereafter remained unchanged. Fibers were superfused with the slow channel blocker, AHR-2666, and the fast channel blocker, tetrodotoxin (TTX). AHR-2666 had age-related effects on AP duration, phase 1 repolarization, plateau height, and time to the peak of the plateau. There were no age-related changes in TTX effects on phases 0--2. In another series of experiments, Purkinje fibers from dogs 23 +/- 1.2 to 106 +/- 1.4 months old were superfused with a calcium-rich solution in which Na+ was replaced by tetraethylammonium (TEA+). The resultant slow response action potentials, which are calcium dependent, showed an age-related decrease in AP amplitude, Vmax, and time to peak amplitude. When these fibers were superfused with the slow channel blocker, verapamil, there was an age-related effect on AP amplitude. Our studies indicate that in the normal aging heart, major changes occur in repolarization that appear, in the main, to result from change in the slow inward current carried by Ca2+.
Release of active and inactive renin by the porcine kidney.
Authors: Bailie M D , Derkx F M , Schalekamp M A
Published: June 2012

We studied the relative rates of release of active and inactive renin by the kidney in anesthetized pigs. Renin concentration was determined in arterial and renal venous plasma as follows: (1) before and after stimulation of renin release with isoproterenol or furosemide, (2) after suppression of renin release by extracellular fluid volume expansion, and (3) after administration of propranolol or indomethacin. Inactive renin was activated by dialysis of plasma at pH 3.3 for 24 hours. Renin concentration was estimated by radioimmunoassay determination of angiotensin I after a 3-hour incubation with excess homologous renin substrate. Following isoproterenol, the release of active renin increased from 8 +/- 4 (SEM) to 58 +/- 34 ng/min, and inactive renin increased from 53 +/- 33 to 321 +/- 136 ng/min. Similarly, furosemide stimulated the release of both active and inactive renin. Both forms of renin were suppressed by propranolol or indomethacin. Although changes in renin release following volume expansion were not statistically significant, the direction of change for both forms of renin was similar. Following logarithmic conversion of the rate of release, the plot of active vs. inactive renin formed a straight line. Values for active renin as a percentage of the total renin in simultaneously drawn arterial and renal venous plasma samples were not different. Thus, under the conditions of these experiments, release of active and inactive renin appears to be controlled by similar mechanisms. Both stimulation and suppression of renin release result in parallel changes in release of the two forms. Data on relative amounts of active renin in arterial and renal venous plasma suggest that there is no systemic conversion of the two forms.
The immediate pressor response to saralasin in man: a test of angiotensin II receptor vacancy.
Authors: Wallace J M , Case D B , Laragh J H , Keim H J , Drayer J I , Sealey J E
Published: June 2012

Saralasin, 10 microgram/kg per min, caused an immediate rise in blood pressure in 52 of 57 (91.2%) hypertensive patients. The increase in diastolic pressure averaged 18.8 +/- 1.83 mm Hg (mean +/- SE) in normal renin patients on a normal salt intake. This immediate pressor response was absent in only five high renin patients and, conversely, was very large in three low renin patients. Direct arterial recordings are necessary to define the response accurately; it begins in 60--90 seconds, peaks in amplitude at 2.05 +/- 0.38 minutes, and subsides over the next 5 minutes in normal renin and high renin patients. The blood pressure elevation is inversely related to background plasma renin activity (r = -0.66, P less than 0.001), and also is directly, but weakly, related to 24-hour urinary sodium excretion (r = + 0.29). Therefore, the amplitude of the elevation is predictably diminished by the rise in plasma renin consequent to prior sodium restriction, and also by preliminary receptor exposure to low dose nonpressor infusions of saralasin itself (0.01-0.1 microgram/kg per min). Phentolamine had no effect on the response in two patients. We propose that the immediate pressor response to saralasin is related directly to the preexisting degree of vacancy of angiotensin II vascular receptors and that the initial agonistic action of the drug may prove useful in defining the angiotensin II receptor status in hypertensive diseases.
Baroreceptor control of atrioventricular conduction in man.
Authors: Mancia G , Bonazzi O , Pozzoni L , Ferrari A , Gardumi M , Gregorini L , Perondi R
Published: June 2012

Although human baroreflexes are known to exert a powerful physiological control on heart rate, little information exists on the physiological control they exert on the atrioventricular conduction system. In 11 normotensive subjects with normal atrioventricular conduction, we altered baroreceptor activity by injection of pressor and depressor drugs (phenylephrine and trinitroglycerin) and recorded mean arterial pressure (MAP, catheter measurements), R-R interval, and pre-His and post-His intervals (A-H and H-V, His bundle recording). With the subjects in sinus rhythm, increasing MAP by 21+/- 1 mm Hg caused a marked lengthening (250 +/- 28 msec), and decreasing MAP by 17 +/- 2 mm Hg a marked shortening (142 +/- 16 msec) of the R-R interval. There was little change in the A-H interval and no change at all in the H-V interval. However, when the R-R interval was kept constant in these subjects by atrial pacing, a similar increase and decrease in MAP caused, respectively, a marked lengthening (49 +/- 6 msec) and shortening (19 +/- 3 msec) of the A-H interval, although the H-V interval remained unaffected. Thus physiological ranges of baroreceptor activation have a marked influence on the atrioventricular node but apparently not on the ventricular portion of the atrioventricular conduction system. This influence is unmasked when pacing prevents the baroreceptor influence on the sinoatrial node.
Reduction of plasma renin activity by inhibition of the fatty acid cyclooxygenase in human subjects: independence of sodium retention.
Authors: Frölich J C , Hollifield J W , Michelakis A M , Vesper B S , Wilson J P , Shand D G , Seyberth H J , Frölich W H , Oates J A
Published: June 2012

We carried out the present studies to determine whether the suppression of plasma renin activity (PRA) that follows inhibition of prostaglandin (PG) synthesis can be dissociated from the sodium-retaining effects of these drugs. In an initial investigation we studied the effect of indomethacin on PRA in normal subjects in balance on a 10 mM Na+ diet to prevent Na+ retention. Under these experimental conditions indomethacin did not lower PRA even though the fatty acid cyclooxygenase was inhibited, as indicated by a greater than 70% reduction in the major urinary metabolite of prostaglandin E (PGE-M). Sodium depletion leads to enhanced sympathetic activity. We therefore studied the effect of indomethacin on a group of subjects in 10 mM Na+ balance in whom the effect of increased beta-sympathetic activity was blocked by the administration of propranolol. In this group, indomethacin caused 65% suppression of PGE-M and had no effect on Na+ balance, but reversibly reduced PRA in the supine and upright positions by 84% and 70%, respectively. In normal subjects in 10 mM Na+ balance, the isoproterenol-induced increase in PRA also was unaffected by indomethacin. These data establish that inhibition of the cyclooxygenase can result in a reduction of PRA that is independent of changes in Na+ balance or beta-sympathetic tone.
Cardiac contractile proteins. Adenosine triphosphatase activity and physiological function.
Authors: Scheuer J , Bhan A K
Published: June 2012

This review has pointed out the good correlation frequently observed between ATPase activity of various contractile protein preparations and contractile function of various muscles including the myocardium. Some of the variables in the measurement of the various ATPases and the relationship of these measurements to physiological ATPase in the intact myofibril have been mentioned. The possible roles of changes in the light chains of sulfhydryl groups in the control of ATPase activity have been outlined. The possibility that phosphorylating reactions might exert control over physiological activity remains to be clarified. It is evident that, despite the large amount of research that has been done, our understanding of how the biochemistry of contractile proteins relates to physiological function is in its infancy, and only with a more complete elucidation of the underlying biochemistry of the components of contractile proteins of physiological and pathophysiological adaptations become evident.
Pulmonary vascular impedance analysis of adaptation to chronically elevated blood flow in the awake dog.
Authors: Hopkins R A , Hammon J W , McHale P A , Smith P K , Anderson R W
Published: June 2012

Pulsatile pulmonary hemodynamics were analyzed in a chronic awake canine high flow model. Standard mean flow and pulsatile flow hemodynamics were measured and alterations in the proximal pulmonary vascular physical properties were quantified by the characteristic impedance (Zo). Pulmonary vascular resistance (PVR), which assesses arteriolar-capillary recruitment of perfusing radius and measures a more distal pulmonary vascular response to changing flows, also was calculated. Twelve control dogs were studied and had mean Qpa (pulmonary blood flow) = 2.02 +/- 0.15 liters/min, Zo = 193 +/- 20 dyne sec cm-5 and PVR = 416 +/- 32 dyne sec cm-5. Ten dogs were studied awake 20 weeks after creation of bilateral arteriovenous fistulae. Five of these shunted dogs, designated group A, developed Qpa = 3-4 liters/min (mean = 3.80 +/- 0.09, P less than 0.001 different from control group); the other five dogs (group B) developed Qpa = 4-8 liters/min (mean = 5.87 +/- 0.16, P less than 0.001). In group A, Zo = 143 +/- 8 (P less than 0.05) and PVR = 249 +/- 6 (P less than 0.10). In group B, Zo = 90 +/- 5 (P less than 0.005) and PVR = 126 +/- 14 (P less than 0.01). The total input power (potential and kinetic) was 125% above the controls for group A (P less than 0.001) and 264% for group B (P less than 0.001), but the mean energy components increased significantly more than did the pulsatile components. These data demonstrate a lower impedance to pulsatile flow during chronically elevated total flow which effects a reduction in both the work load of the right ventricle and the transmission of energy to the precapillary bed. Analysis of the alterations in characteristic impedance suggests a distinct proximal pulmonary vascular mechanism of decreased vessel stiffness (decreased elastic moduli) for adaptation to chronically elevated flow loads which is in addition to the two geometric alterations of proximal arterial dilation and distal vascular channel recruitment.
Circus movement in canine right ventricle.
Authors: de Bakker J M , Henning B , Merx W
Published: June 2012

The present study reports on the epicardial spread of excitation during premature beats and during the initial stages of ventricular fibrillation, both of which were induced by single-test stimuli during regional ischemia or local hypothermia. Simultaneous recording of the activity at 48 epicardial sites on the right ventricle of dog hearts enabled us in some instances to demonstrate a circus movement.
Suppression of renin secretion in the rat kidney by a nonvascular alpha-adrenergic mechanism.
Authors: Vandongen R , Strang K D , Poessè M H , Birkenhäger W H
Published: June 2012

We studied the effect of alpha-adrenergic stimulation, using phenylephrine, on basal and isoproterenol-provoked renin secretion in the isolated perfused rat kidney. Infusion of phenylephrine increased renal perfusion pressure and prevented the response in renin secretion to isoproterenol. No suppression of basal secretion was observed. Renal vasoconstriction was abolished, and the response in renin secretion to isoproterenol was restored by alpha-adrenoceptor blockade with phenoxybenzamine. In contrast, when renal vasoconstriction was prevented by dihydralazine, suppression of renin release by phenylephrine still occurred. These observations support an inhibitory effect of a nonvascular alpha-adrenergic mechanism on renin release. We suggest that the alpha receptor mediating this effect is related directly to the juxtaglomerular cell.
Correlation of function and morphology of neonatal rat and embryonic chick cultured cardiac and vascular muscle cells.
Authors: Marvin W J , Robinson R B , Hermsmeyer K
Published: June 2012

To develop morphological criteria which can be applied systematically for the identification of isolated cardiac and vascular muscle cells in mammalian and avian primary cultures, we have correlated structural and staining properties with excitability, contraction, and norepinephrine sensitivity of isolated muscle cells. The primary cultures of cardiac and vascular muscle contained muscle cells and nonmuscle cells. The muscle cells could be clearly identified by action potentials, contractility, and Masson's trichrome stain characteristics, similar to those of cells from intact source heart and blood vessels. Furthermore, the muscle cells were highly responsive to norepinephrine, showing unequivocal increases in contraction frequency. The sensitivity to norepinephrine was found to be very high (ED50 = 2.3 X 10(-9) M) Phase-contrast observation was sufficient to identify muscle cells only when those cells were contracting. There were no unequivocal morphological characteristics that distinguished between quiescent muscle cells and nonmuscle cells in the absence of histochemical staining. Ultrastructural examination by scanning electron microscopy failed to distinguish between muscle and nonmuscle cells. Histological staining was, therefore, the only reliable nonfunctional identification process that separated muscle cells from nonmuscle cells. Primary cultures, containing nonmuscle as well as muscle cells, are an important experimental preparation because the cellular heterogeneity probably minimizes muscle cell loss of function and phenotypic changes. The correlation we have established between cell staining and function will facilitate exploration of single cell properties, which together constitute hearts and blood vessels.
Effects of the oral converting enzyme inhibitor, SQ 14225, in a model of low cardiac output in dogs.
Authors: Freeman R H , Davis J O , Williams G M , DeForrest J M , Seymour A A , Rowe B P
Published: June 2012

Dogs with thoracic caval constriction retain sodium and develop ascites and edema. The role of the renin-angiotensin-aldosterone system in this model of low output failure was evaluated before, during, and after administration of the new orally active converting enzyme inhibitor, 2-D-methyl-3-mercaptopropanoyl-L-proline (SQ 14225). The acute response to the initial oral dose of SQ 14225 (10 mg/kg) consisted of a striking fall in plasma aldosterone concentration (PAC) from 22.7 and 29.9 ng% to 10.7, 11.9, and 11.0 ng% (P less than 0.05) after 67.5, 112.5, and 157.5 minutes; sodium excretion increased from 1.9 and 1.9 mu Eq/min to 19.9, 22.4, and 17.8 mu Eq/min. Arterial pressure and filtration fraction decreased (P less than 0.05), and plasma renin activity (PRA) increased (P less than 0.05) after the initial dose of SQ 14225; clearance of paraaminohippuric acid (PAH) and creatinine did not change significantly. The daily responses for 3-4 days to SQ 14225 (35 mg/kg per day, given as doses of 10, 10, and 15 mg/kg) were a decrease in PAC from 50 +/- 15 and 32 +/- 10 ng% to 10 +/- 4 ng% on the 4th day, a value not statistically different from normal (P greater than 0.05), and an increase in sodium excretion from 2.9 to 2.0 mEq/day to 5.7, 10.0, 32.4, and 32.9 mEq/day on a sodium intake of 35 mEq/day (P less than 0.05 for the last 2 days). Arterial pressure and creatinine clearance decreased (P less than 0.05). PRA increased transiently on day 1 of SQ 14225 and then returned toward control levels, and clearance of PAH was unchanged. These data demonstrate an important role for aldosterone and the renin-angiotensin system in the retention of sodium and in ascites formation in dogs with thoracic caval constriction.