bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of prostaglandins in the reversal of one-kidney hypertension in the rabbit.
Authors: Romero J C , Ott C E , Aguilo J J , Torres V E , Strong C G
Published: June 2012

Hypertensive rabbits with a clip on the renal artery of their solitary remaining kidney show an abrupt decrease in blood pressure after the arterial constriction is released. Although the mechanism underlying this phenomenon remains controversial, some experimental evidence suggests that it could be humorally mediated. The involvement of prostaglandins was investigated by examining the effect of the release of the arterial constriction on blood pressure, renal blood flow, glomerular filtration rate, and urinary output in five conscious single-kidney hypertensive rabbits in which prostaglandin synthesis was blocked with indomethacin (priming intravenous injection of 9 mg/kg followed by a constant infusion of 1 mg/kg hour-1). The results were compared with those obtained in another group of five single-kidney hypertensive rabbits submitted to the same protocol but not treated with indomethacin. The blockade of prostaglandin synthesis with indomethacin prevented the increments in renal blood flow and glomerular filtration rate seen in the control rabbits after unclipping a significantly retarded the appearance of diuresis and the fall in blood pressure. Despite these observations, the results do not indicate a major participation of prostaglandins in the reversal of single-kidney hypertension, because the decrease in blood pressure 9 hours after the removal of the arterial constriction was similar in both groups.
In vivo determination of cerebral blood volume with radioactive oxygen-15 in the monkey.
Authors: Eichling J O , Raichle M E , Grubb R L , Larson K B , Ter-Pogossian M M
Published: June 2012

A method for the in vivo determination of cerebral blood volume was tested in 15 adult rhesus monkeys. The technique utilized external residue detection and required the serial measurement of two mean transit times, namely, that of an intravascular tracer, C15O-hemoglobin, and that of a diffusible tracer, H215O. In computing the mean transit time for the intravascular tracer, the conventional Hamilton extrapolation of the downslope of the recording obtained for the washout of the tracer from the brain subsequent to an intracarotid bolus injection was found to be inadequate, yielding a mean transit time that systematically underestimated that parameter. Alternatively, the use of a power law extrapolation, as proposed by Huang, allowed a more accurate prediction of the vascular mean transit time. The preliminary studies testing the method predicted that the relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) was adequately represented by the equation CBV = 0.80CBF0.38, with a correlation coefficient of r = 0.90 for the cerebral blood flow range of 16 to 134 ml/100 g min-1 with a normocapnic cerebral blood volume of 3.5 ml/100 g perfused brain tissue (arterial Pco2 = 37 torr, CBF = 50 ml/100 g min-1).
Anaylsis of ventricular activation and repolarization from intramural and epicardial potential distributions for ectopic beats in the intact dog.
Authors: Spach M S , Barr R C
Published: June 2012

Ventricular activation and repolarization were examined by measuring intramural and epicardial potential distributions during ectopic sequences in intact dogs. Potential distributions were used because they provided a direct measure of all of repolarization. Ectopic sequences produced almost unidirectional excitation across the heart along with repolarization events that were different from normal. During ectopic repolarization, positive potentials occurred over a broad area surrounding the ectopic focus, and negative potentials occurred over a large area on the opposite side of the heart where excitation terminated. The potentials in the walls of both ventricles were more positive in the outer layers and more negative in the inner layers, a gradient similar to normal. A maximum initially was at the ectopic site with a magnitude greater than that of the minimum, but the maximum subsequently decreased in magnitude and shifted toward the minimum while the minimum increased in magnitude. The steepest gradients were initially around the maximum, and they then shifted toward the minimum. The results show that ventricular repolatization potential distributions during ectopic beats are predominantly influenced by gradients from one side of the heart to the other (transventricular gradients) in contrast to normal repolatization distributions which are predominantly influenced by gradients across the wall (transmural gradients).
The response of atrial stretch receptors to increases in heart rate in dogs.
Authors: Zucker I H , Gilmore J P
Published: June 2012

The discharge characteristics of type B left atrial receptors were analyzed during alterations in heart rate. Recordings were made from single-fiber preparations of the left cervical vagus of pentobarbital-anesthetized, open-chest dogs. The heart was paced following a sinoatrial crush at frequencies ranging from 60 to 240 beats/min. Left atrial transmural pressure was varied at each heart rate by the intravenous infusion of warm isotonic NaCl. As heart rate was increased there was a progressive decrease in the level of peak "v" wave left atrial pressure. Concomitantly with the decrease in left atrial pressure, the number of spikes per cardiac cycle decreased as did the maximal instantaneous frequency of discharge. A significant positive relationship could be demonstrated with either the discharge per minute [(spikes per cycle) X heart rate] or discharge per cycle vs. the peak "v" wave of the left atrial pressure, regardless of heart rate. The number of impulses that entered the central nervous system per unit of time remained relatively constant at heart rates between 90 and 240/min. It is concluded from these data that the reflex effects which have been attributed in the past to atrial stretch receptor stimulation during clinical episodes of atrial tachyarrhythmias may be better correlated with some aspect of receptor discharge other than frequency or the number of discharges per cycle.
The role of angiotensin in the canine renal vascular response to barbiturate anesthesia.
Authors: Burger B M , Hopkins T , Tulloch A , Hollenberg N K
Published: June 2012

The influence of barbiturate anesthesia on renal blood flow was assessed by the xenon washout method in trained dogs with catheters chronically implanted in the renal artery. Anesthesia induced with either thiopental sodium or pentobarbital sodium resulted in a striking reduction in renal blood flow (4.1 +/- 0.1 vs. 2.6 +/- 0.2 ml/g per min; P less than 0.001) without a change in arterial pressure. The reduction in blood flow was prevented by a high salt intake and partially reversed by agents which interrupt the renin-angiotensin system (BPF 9a; 1-Sar,8-Ala-angiotensin II; propranolol) but not by alpha-adrenergic blocking agents (phentolamine and phenoxybenzamine). Anesthesia blunted the renal vascular response to angiotensin II (P less than 0.0005) whereas responsiveness to norepinephrine was increased (P less than 0.05). We conclude that barbiturate anesthesia induces a major, angiotensin-mediated renal vascular response which must be considered in the interpretation of experiments performed under these conditions.
The relationship between age and relaxation of vascular smooth muscle in the rabbit and rat.
Authors: Fleisch J H , Hooker C S
Published: June 2012

Relaxation of rabbit and rat aorta by isoproterenol decreases with increasing age, whereas such responses caused by nitroglycerin or sodium nitrite are not age-dependent. In the present study, we sought to determine whether this relationship also exists in pulmonary arteries and portal veins. As was the case with the aorta, isoproterenol-induced relaxation of pulmonary arteries decreased as the animal aged; relaxation by nitroglycerin was minimally altered. Aging did not influence responses of rabbit and rat portal veins to isoproterenol or nitroglycerin. If the responses of these blood vessels are characteristic of the responses of other vascular smooth muscles to vasodilators, then this study suggests a difference in the manner by which arteries and veins age. We also confirmed that isoproterenol-induced relaxation of rabbit and rat aorta markedly decreases with increasing age and that the responses of rat aorta to nitroglycerin are independent of age. Because of the agonist used to contract the tissues prior to drug-induced relaxation, the results of the first series of experiments with nitroglycerin on rabbit aorta were at variance with our earlier findings. When KCl was used to contract the aortas, the mean effective dose (ED50) obtained for nitroglycerin for tissues from 2-year-old rabbits was 8 to 19 times larger than that obtained from 2-month-old rabbits. This ratio dropped to 4 when the tissues were contracted with histamine. Since KCl and histamine contract rabbit aorta by different mechanisms, this finding suggests that, in addition to a specific loss in beta-receptor activity, increasing age results in an alteration in the contraction-relaxation process of rabbit aortic tissue.
Length-induced changes in activation during contraction. A study of mechanical oscillations in strontium-mediated contractions of cat and frog heart muscle.
Authors: Henderson A H , Cattell M R
Published: June 2012

The plateau phase of prolonged Sr-mediated contractions of preparations of cat and frog heart muscle was used to study the transient response to abrupt changes in load or length. An oscillatory response (total amplitude equal to or less than 5% Lmax) was obtained. Isotonic oscillations were less damped than their isometric counterparts, implying positive feedback and thus a causal role of the perturbation in length. Oscillation frequency was 2-3 HZ at 29 degrees C (Q 10, 2-3); it could be increased by epinephrine or caffeine, independently of their effects on extent of shortening; it otherwise changed as a generally constant function of the length at which the oscillation occurred, whether this was altered by changes in extracellular [Sr], frequency of contraction, or load (independent of the direction and magnitude of the preceding load step). Similar oscillatory responses were induced during Sr- or Ca-mediated contractures. Cat muscles showed an additional slower component to the oscillatory response. Transient augmentation of the velocity-length relationship after abrupt reduction in load, previously described for twitch contractions under certain conditions, appears to be analogous to the first phase of the oscillatory response studied here. Our findings indicate that the oscillation is not attributable to any mechanism intrinsic to myofilament interaction, but rather that it involves length-induced changes in the level of activation, probably mediated by Ca2+ or Sr2+. We conclude that length influences the level of activation during contraction of heart muscle.
The pumping ability of the left heart and the effect of coronary occlusion.
Authors: Elzinga G , Westerhof N
Published: June 2012

In an isolated preparation of cat heart we studied the pumping capacity of the left heart while left atrial filling pressure was kept constant. We used the source impedance concept to quantify the pumping capacity. In this source impedance concept the relation between left ventricular output and left ventricular pressure is given by the formula (see article) where Zs = source impedance, Plv = left ventricular pressure, Iao = flow in the ascending aorta, and omega = 2pif, f being frequency.. The pressure obtained at zero flow is called the hydromotive pressure (HMP). Only the mean values of pressure and flow were studied. We studied the behavior of 10 hearts in three different experimental situations and in the following sequence: (1) control conditions, (2) after ligating a part of the left coronary arterial system, and (3) after restoring left ventricular output to control level by raising left atrial filling pressure. It was found that source resistance was not significantly different in the three situations but that mean hydromotive pressure (HMP) was significantly lower after ligation of a part of the left coronary arterial system. It was concluded that the decrease in pumping capacity of the left heart after infarction can be compensated for almost completely by an increase in left atrial filling pressure. This compensating mechanism therefore seems to be very efficient.
Evidence for a renal alpha-adrenergic receptor inhibiting renin release.
Authors: Pettinger W A , Keeton T K , Campbell W B , Harper D C
Published: June 2012

The mechanism by which clonidine suppresses renin release was investigated in conscious rats. This suppression was studied by means of selected autonomic interventions in conjunction with changes in sodium balance. Serum renin activity and direct arterial pressure were monitored. Clonidine administration suppressed basal (by 68-85%), diuretic-induced (by 89%), and sympathetic nervous system-mediated (by 75-100%) renin release. Cholinergic, ganglionic, and peripheral sympathetic neuronal blockade did not prevent this inhibitory effect of clonidine. These results indicate a peripheral site of action for suppression of renin release by clonidine. The alpha-adrenergic blocking drug phentolamine prevented clonidine suppression of renin release in sodium-depleted rats and was partially effective in normal rats. Phentolamine blocked the decrease in renin caused by clonidine in ganglion-blocked rats. Clozapine, a new neuroleptic agent with alpha-adrenergic blocking activity, or phenoxybenzamine blocked the effect of clonidine on renin release in both sodium-depleted and normal rats. After ganglionic blockade in sodium-depleted rats, clonidine caused a significantly greater suppression of renin release than did an equipressor dose of methoxamine. These data, combined with hemodynamic correlates, suggest that clonidine inhibits renin release by activation of an intrarenal alpha-adrenergic receptor.
Vascular capacitance and fluid shifts in dogs during prolonged hemorrhagic hypotension.
Authors: Rothe C F , Drees J A
Published: June 2012

The mean circulatory pressure (Pmc) in dogs anesthetized with chloralose-urethane was estimated from 0.5 to 150 minutes after hemorrhages of 0, 17, or 34 ml/kg, or that volume giving an arterial pressure (Pa) of 40 mm Hg. The Pmc was determined by fibrillating the heart and then rapidly pumping blood from aorta to vena cava until Pa=venous pressure (Pv)=Pmc. Within about 10 seconds, the heart was defibrillated. Vascular compliance was estimated as the ratio of a test blood volume change (0, +/- 8.5, or 17 ml/kg) to the change in Pmc, determined 0.5 minute after the start of the test volume change. Erythrocyte and plasma volumes were measured by 51Cr-erythrocyte and 125I-albumin dilution. In response to prolonged hemorrhage: (1) the total vascular compliance apparently decreased; (2) most of the changes in capacity vessels occurred within 5 minutes, and indeed a large part of the response probably had occurred by the time of the first measurement at 30 seconds; (3) the progressive recovery in Pmc after 5 minutes was primarily from fluid shifting into the vasculature; (4) even after 2 hours of severe hemorrhagic hypotension, the venoconstriction was not lost; but (5) after an hour of severe hemorrhagic hypotension (arterial pressure of 40 mm Hg) there was water loss from the vasculature, because plasma protein and erythrocyte concentrations and plasma oncotic pressure increased.
Regional myocardial blood flow during acute myocardial infarction in the conscious dog.
Authors: Bishop S P , White F C , Bloor C M
Published: June 2012

Regional myocardial blood flow was studied in the conscious dog at periods of 5 minutes to 4 days after occlusion of a major branch of the left coronary artery. Dogs were instrumented with aortic electromagnetic flow probes, occlusive cuffs on either the anterior descending or circumflex branch of the left coronary artery, and a left atrial Silastic catheter for injection of microspheres (15 +/- 5 mum) labeled with either 85Sr, 141Ce, or 51Cr. Microspheres were injected into 25 fully conscious dogs during three of the following time periods: control preocclusion and 0.1, 2, 6, 24, or 96 hours postocclusion. In the conscious dog, before occlusion, the endocardial half of the left ventricular myocardium received 28% more blood flow than the epicardial half. After sudden occlusion of a coronary artery branch, there was a marked reduction in blood flow as well as an alteration in distribution of blood flow within the ischemic tissue; blood flow was most severly reduced in the subendocardial center of the ischemic region, less so in the epicardial ischemic region, and least reduced in the marginal region of the infarct. Blood flow was increased to the nonischemic tissue. There was no change in this pattern of reduced blood flow by 6 hours postocclusion, but by 24 hours, flow was moderately increased to all areas except the central subendocardial core, and was further increased at 96 hours. Blood flow to the endocardial half of the left ventricular myocardium averaged 63 ml/100 g per min during the control period, was reduced to 12-18 ml/100 g per min at 0.1-6 hours in the ischemic region, increased to 29 ml/100 g per min at 24 hours, and to 48 ml/100 g per min by 96 hours. These findings indicate that there is a reversal of the flow ratio within ischemic myocardium with relative under-perfusion of the endocardial half of the wall, which is not corrected by 4 days. There is a modest increase of collateral blood flow to ischemic tissue by 24 hours and this increase is considerably augmented by 96 hours, apparently as a result of the growth and enlargement of collateral vessels.
Spinal adrenergic mechanisms regulating sympathetic outflow to blood vessels.
Authors: Taylor D G , Brody M J
Published: June 2012

The role of descending spinal catecholamine (CA)-containing fibers in cardiovascular regulation was examined. Monoamine-containing fibers were visualized by fluorescence histochemical methods at the cervical, thoracic, and lumbar spinal segments. Two major groups of descending CA-containing axons were located in the lateral funiculus at the midcervical spinal level. At the thoracolumbar spinal segments CA-containing terminals were concentrated mostly around cells of the intermediolateral nucleus. In addition a distinct CA-containing fasciculus was observed at the level of the sympathetic nucleus which appeared to course toward the opposite site of the cord. To evaluate the role of the efferent CA-containing fibers, changes in heart rate, arterial pressure, femoral blood flow, and calculated peak vascular resistance were elicited by electrical stimulation of selected sites in the midcervical spinal cord. Although changes in femoral flow and arterial pressure were evoked from many midcervical sites, there was a distinct correlation between the magnitude of peak femoral resistance elevation and density of CA-containing axons activated. Furthermore, efferent spinal vasoconstrictor outflow to the hindlimbs crosses below the cervical level. This observation is in good agreement with fluorescence microscopy studies revealing CA-containing fibers which appear to decussate. Pharmacological studies also were undertaken to evaluate transmission in spinal vasopressor pathways. In these studies alpha-adrenergic receptor antagonists and agonists were perfused into the spinal subarachnoid space. Heart rate, arterial pressure, femoral flow, and femoral resistance responses elicited from efferent spinal pathways were significantly attenuated following superfusion of the spinal cord with the alpha-antagonists BE-2254 (HEAT) and phentolamine. It was shown that inhibition of the centrally evoked responses was due to actions of the alpha-antagonists at a spinal locus and not due to peripheral vascular alpha-receptor blockade. Spinal perfusion with the alpha-receptor agonist norepinephrine potentiated cardiovascular responses. Likewise, loading with the norepinephrine precursor 3,4-dihydroxy-L-phenylalanine (L-dopa) enhanced vasoconstrictor responses evoked in the cross-perfused hindlimb of p-chlorophenylalanine-pretreated cats. These observations support the idea that bulbospinal CA-containing fibers relay excitatory impulses to preganglionic vasoconstrictor neurons and that spinal alpha-adrenergic receptor activation is necessary for transmission of this information.
Receptor binding of angiotensin II and antagonists. Correlation with aldosterone production by isolated canine adrenal glomerulosa cells.
Authors: Douglas J , Saltman S , Fredlund P , Kondo T , Catt K J
Published: June 2012

The binding properties of the angiotensin II receptors of the adrenal cortex have been studied in isolated cells prepared by collagenase dispersion of the zona glomerulosa of the canine adrenal gland. Such cell preparations are responsive to physiological concentrations of angiotensin II, and permit correlation of binding of angiotensin II and its analogues with aldosterone production in vitro. Uptake of 125I-angiotensin II (5 X 10(-11) M) by glomerulosa cells at 37 degrees C reached a steady state at 45 minutes, with a subsequent plateau for at least 60 minutes. Angiotensin II binding was also dependent upon the hormone and cell concentrations employed during uptake studies. Bound angiotensin II was rapidly dissociated from canine adrenal cells after addition of the unlabeled octapeptide. High affinity sites with equilibrium association constant (Ka) of 3.3 X 10(9) M-1 comprised 25-33% of the receptor population and the remainder of the sites were of lower affinity, 2.5 X 10(8)M-1. Binding of angiotensin II analogues and antagonists was found to be consistent with their biological activities. The analogue most extensively evaluated was [Sar-1]angiotensin II, which exhibited enhanced binding activity when compared to angiotensin II, and had a higher equilibrium association constant by kinetic analysis and direct binding studies. Direct binding of labeled angiotensin II to the adrenal glomerulosa receptor has been correlated with a progressive response in aldosterone production. The steroidogenic response to angiotensin II was maximal when 25% of the receptor population was occupied; this fraction corresponds to the proportion of high affinity receptor sites measured by binding analysis. In addition, inhibition of angiotensin II binding to receptor sites by the competitive antagonist [Sar-1, Ala-8]angiotensin II has been correlated with inhibition of aldosterone production. These findings serve to demonstrate the biological significance of the angiotensin II binding sites of the adrenal cortex, and confirm their role as receptors which mediate the steroidogenic responses to angiotensin II.
Angiotensin II and angiotensin III in rat blood.
Authors: Semple P F , Morton J J
Published: June 2012

Angiotensin II and its metabolites, [des-Asp-1]-angiotensin II (angiotensin III), [des-(Asp-1,Arg-2)]angiotensin II, and [des-(Asp-1,Arg-2,val-3)]angiotensin II, were measured in arterial and venous plasma from normal rats. Paper chromatography was used to separate the peptides which were measured with a radioimmunoassay method using an angiotensin II antiserum which had a 100% cross-reaction with each of these metabolites. A mean of 33% of the immunoreactive material in arterial plasma was angiotensin II, 58% angiotensin III, and 9% [des-(Asp-1,Arg-2)]angiotensin II/[des-(Asp-1,Arg-2,Val-3)]angiotensin II. A similar distribution was found in venous plasma. This and other evidence indicates that angiotensin-induced aldosterone secretion in the rat, unlike that in other mammalian species so far studied, may be mediated by angiotensin III.
Enhanced aldosterone response to angiotensin II in human hypertension.
Authors: Kisch E S , Dluhy R G , Williams G H
Published: June 2012

Adrenal and vascular responsiveness to graded doses of angiotensin II (A II) were recorded for seven normal subjects and 12 patients with essential hypertension while in balance on an intake of 200 mEq sodium/100 mEq potassium. Patients with essential hypertension had been previously studied and known to have normal responses of plasma renin activity to sodium restriction and upright posture. A II was administered for 30 minutes at rates of 0.1, 0.3, 1, and 3 ng/kg per minute and plasma aldosterone responses were assessed 20 and 30 minutes later; blood pressure was monitored at intervals of 1 minute during infusion of A II at each rate. A significant increment in plasma aldosterone occurred at an infusion rate of 0.3 ng/kg per minute in patients with hypertension. This change was not seen until the infusion rate reached 1.0 ng/kg per minute in the normotensive control subjects. Even at an A II infusion rate of 1 ng/kg per minute, the increment in plasma aldosterone levels in normotensive subjects (4.2 +/- 0.6 ng/dl) was significantly less (P less than 0.001) than that in patients with essential hypertension (19 +/- 3 ng/dl). In both groups, a significant rise in mean arterial blood pressure occurred at an A II dose of 0.3 ng/kg per minute, but the pressor response of the hypertensive group was significantly greater at the highest infusion rate (3 ng/kg per minute) (P less than 0.05). Thus, enhanced adrenal and pressor responsiveness to infused A II was observed in the hypertensive subjects, suggesting a change in A II receptor affinity.
Basal vascular tone in the kidney. Evaluation from the static pressure-flow relationship under normal autoregulation and at maximal dilation in the dog.
Authors: Gross R , Kirchheim H , Brandstetter K
Published: June 2012

In conscious dogs static pressure-flow relationships (I-P curves) were obtained both for the normal autoregulating kidney vasculature and under conditions of maximal vasodilation induced by infusion of papaverine or acetylcholine into the renal artery. Concentration-response curves for the substances infused showed the typical S-shape. Control I-P curves exhibited an autoregulatory plateau; under maximal vasodilation the I-P curves were pressure-passive up to a perfusion pressure of 50 mm Hg, following a power function (1 = a-Pn) with an exponent greater than 1. Under the influence of acetylcholine, renal blood flow was significantly higher than under control conditions even at a perfusion pressure of 20 mm Hg. This indicates that there is an appreciable vascular tone even at a low pressure. The I-P curves under acetylcholine showed a break at about 50 mm Hg, above which the I-P curves were straight lines.
Cellular basis for increased sensitivity of vascular smooth muscle in spontaneously hypertensive rats.
Authors: Hermsmeyer K
Published: June 2012

There is evidence that hypersensitivity of vascular muscle to neurotransmitters contributes to the development of hypertension. Comparison of the caudal arteries of spontaneously hypertensive rats (SHR) and their genetically related Kyoto-Wistar normotensive control rats (KNR) showed that although there is no difference in membrane potential under unstimulated conditions, greater depolarization of the SHR vascular muscle cells by norepinephrine occurs at concentrations which cause greater contraction. The mechanism for the increased depolarization and resulting increase in contraction appears to be a lower intracellular potassium ion activity in SHR vascular muscle cells, which results in a lower contribution of potassium gradient to membrane potential. Experiments to determine the sensitivity of isolated, dispersed chick omphalomesenteric vascular muscle cells to neurotransmitters showed remarkably low thresholds to the neutransmitters norepinephrine, serotonin, and acetylcholine, but not potassium chloride. The high sensitivity of isolated cells to neurotransmitters suggests that factors in the intact vessel may cause thresholds to be high, possibly implying that alterations in a neurotrophic mechanism might be responsible for changes in vascular muscle sensitivity in situ.
Modification of the flow-generating capability of the canine heart-lung compartment by the carotid sinus baroreceptor reflex.
Authors: Kostiuk D P , Sagawa K , Shoukas A A
Published: June 2012

To quantitatively understand how the carotid sinus baroreceptor reflex modifies the Starling curve (i.e., the aortic flow (AF)-mean right atrial pressure (MRAP) relationship), experiments were performed in closed-chest, naturally breathing, and anesthetized dogs before and after vagotomy. Mean aortic pressure (MAP) was fixed at approximately 100 mm Hg and the pressure in the isolated carotid sinus (ISP) was varied from 75 to 150 mm Hg in steps of 25 mm Hg. At each ISP, MRAP was slowly increased and decreased while measuring AF by a previously implanted electromagnetic flow probe. A family of AF-MRAP relation curves specified at the different ISP's were thus obtained. Third-order polynomials in MRAP and ISP adequately fit these curves. Whether the vagi were intact or cut, there was no significant difference between the AF-MRAP relation curves obtained at an ISP of 75 or 100 mm Hg. However, decreasing ISP from 125 to 100 mm Hg caused a 24% increase in AF, and increasing ISP to 150 mm Hg caused a 15% decrease in AF in the dogs with intact vagus nerves. For the vagotomized dogs, the same decrease or increase in ISP caused a 17% increase or a 21% decrease in AF, respectively. When MAP was allowed to change by the reflex, only insignificant changes in AF occurred. We conclude that the carotid sinus reflex significantly alters the flow-generating ability of the heart-lung compartment by as much as 40% but this becomes clearly observable only if the reflex change in aortic pressure is prevented.
Aggravation of atherosclerosis by hypertension in a subhuman primate model with coarctation of the aorta.
Authors: Hollander W , Madoff I , Paddock J , Kirkpatrick B
Published: June 2012

The interrelationships between hypertension and atherosclerosis were investigated in a subhuman primate model (cynomolgus monkey) with hypertension produced by surgically coarcting the miathoracic aorta. The hypertensive coarcted monkey fed a low cholesterol diet for 6 months did not develop complicating atherosclerosis but did develop focal intimal lesions as well as marked thickening of the musculoelastic media of both the large and small arteries. Fibrocellular thickening of the intima and media occurred in the vessels proximal to the coarctation but not distal to the coarctation suggesting that a high level of blood pressure with resulting increase in arterial wall tension is responsible for these changes. The hypertensive coarcted monkey fed a hypercholesterolemic diet (2% cholesterol and 10% butter) for 6 months developed severe coronary atherosclerotic disease with fibrous plaque formation. The disease produced over 65% luminal narrowing of the major coronary arteries and their extramural and intramural branches. In contrast the noncoarcted normotensive animal fed the same diet developed mild atherosclerosis of only the major coronary arteries which caused an average luminal narrowing of 12%. Aggravation of atherosclerosis by hypertension also appeared to occur in the other arteries above the coarctation particularly the cerebral arteries. When the hypertensive coarcted monkey with preestablished coronary atherosclerosis was treated with a low cholesterol diet and a combination of antihypertensive drugs (hydrochlorothiazide, hydralazine, and reserpine), the progression of the disease was arrested. There also was evidence that treatment caused some regression of the coronary lesions which appeared to "heal" by fibrosis. The treatment of both hyperlipidemia and hypertension appeared to be more effective than the treatment of hyperlipidemia, alone.
Studies on membrane-bound renin in the mouse and rat.
Authors: Wilson C M , Ward P E , Erdös E G , Gecse A
Published: June 2012

Membrane-bound renin was isolated from the submaxillary gland and kidney of the white Swiss Webster mouse and from the kidney of the rat. Administration of the male sex hormone testosterone or an anabolic steroid, such as nandrolone phenpropionate (Durabolin), induces renin activity in microsomal fraction of the submaxillary gland of the young female mouse. Actinomycin D blocks this induction partially. Renin that sedimented with the microsomal fraction was isolated from the homogenized kidney of the mouse by density gradient centrifugation. Microsomal renin was also isolated from rat kidney disrupted by the N2 cavitation technique. The enzyme in the microsomal fraction that had been washed extensively was only partially active, but freezing and thawing or Triton X-100 activated microsomal renin. The same microsomal fraction contained active kallikrein. In pilot studies a plasma membrane-enriched fraction was isolated from the microsomal fraction of the homogenized rat kidney cortex that had both renin and kallikrein activity.
Evidence that des-Asp1 angiotensin II mediates the renin-angiotensin response.
Authors: Freeman R H , Davis J O , Lohmeier T E , Spielman W S
Published: June 2012

Studies were undertaken to compare and evaluate the influence of angiotensin II and its heptapeptide fragments, des-Asp-1-angiotensin II, at various receptor sites for angiotensin in both dogs and rats. Receptor sites evaluated were those which are found in the glomerulosa, reticularis, and fasiculata of the adrenal cortex, in the renal arterioles and the juxtaglomerular cells of the kidney, and in the peripheral arterioles. Both peptides produced similar changes in the steriod secretion profiles for aldosterones, corticosterone, and cortisol in the dog. In the rat, both peptides similarly increased aldosterone and corticosterone secretion; however, a larger dose of the competitive antagonist Sar-1,Ala-8-angiotensin II was required to block the steroid response to the heptapeptide. This finding suggests that receptor affinity for des-Asp-1-angiotensin II may be greater than its affinity for angiotensin II. Both peptides also decreased renin secretion and renal blood flow similarly in the dog. The pressor response to the heptapeptide was only about one-half the pressor response to angiotensin II in both the rat and dog studies. Collectively, these observations in dogs and rats suggest that des-Asp-1-angiotensin II may mediate the response to the renin-angiotensin system at both adrenal and renal receptors.
Studies on the nature of a prostaglandin receptor in canine and rabbit vascular smooth muscle.
Authors: Greenberg S , Kadowitz P J , Long J P , Wilson W R
Published: June 2012

The contractile response of rabbit renal arteries and canine tibial arteries to prostaglandins A2, B2, F2alpha, E1, E2, D2, and B1 was associated with a reduction in total sulfhydryl group content of smooth muscle. The total sulfhydryl content of rabbit renal and canine tibial arteries and was not affected by norepinephrine or potassium chloride. Reduction of disulfide groups with dithiothreitol (DTT) selectively inhibited contractile responses to angiotensin and prostaglandins; 5,5'-Dithiobisnitrobenzoic acid (DTNB), a sulfhydryl group-oxidizing agent, reversed the inhibitory effect of DTT on the contractile responses to prostaglandins. Alkylation of free sulfhydryl groups with ethacrynic acid did not affect the contractile response of isolated canine tibial or rabbit renal arteries to any agonist studied. Ethacrynic acid added to muscle strips exposed to DTT resulted in alkylation of sulfhydryl groups produced by reduction of disulfide bonds and irreversibly prevented DTNB-induced reversal of DTT inhibition of contractile responses to prostaglandins. However, addition of ethacrynic acid to muscle strips contracted by prostaglandins did not inhibit subsequent responses to these acidic lipids. These findings support the hypothesis that contractile responses of rabbit renal and canine tibial arteries to prostaglandins are dependent on interactions between prostaglandins and disulfide groups located in or on the vascular smooth muscle cell, and the concept that membrane disulfide groups may be integral components of vascular smooth muscle receptors for prostaglandins.
The low frequency dynamic viscoelastic properties of human aortic valve tissue.
Authors: Lim K O , Boughner D R
Published: June 2012

Membranous samples of human aortic valve cusps were subjected to sinusoidal fluid pressure variations (frequency range, 0.5-5 Hz) to assess their dynamic viscoelastic properties. The storage (elastic) and loss (viscous) moduli and phase lag between the stressing function and response were found to be independent of the frequencies applied. The respective average values were 1.35 (SE = 0.06) X 10(8) dynes cm-2, 4.14 (SE = 0.28) X 10(6) dynes cm-2, and 0.033 (SE = 0.002) rad. The small phase lag indicates that the tissue would recover almost completely to its original state on removal of any applied stress, and this and the relatively low extensibility should be considered in the design of leaflet-type valve prostheses. The storage modulus of the aortic valve cusps when compared to that of the mitral leaflet shows the mitral leaflet to be almost twice as stiff as the aortic valve cusps. This finding led us to conclude that the vibrations of these two cardiac valves alone cannot contribute in any significant way to the production of the observed lower frequency of the first and the higher frequency of the second heart sounds and that other factors must be considered to explain this finding.
Myocardial tissue recruitment in the dog as determined by double tracer dilution method.
Authors: L'Abbate A , Mildenberger R R , Zborowska-Sluis D T , Klassen G A
Published: June 2012

The amount of tissue perfused, as determined from the difference in volume of distribution between a diffusible indicator (125I-antipyrine) and an intravascular indicator (131 I-albumin) was measured at different values of coronary flow, perfusion pressure, and vasomotor tone in the working left ventricle of an open-chest dog. Coronary pressure and flow were regulated independently from the systemic circulation and coronary vasomotor tone was reduced by dipyridamole. At each flow vasomotor tone was assessed by using as a reference the maximal vasodilation induced by arrest of flow. Measured tissue space was considered to be related to the capillary surface area available for tracer diffusion and therefore to the number of perfused capillaries per volume of muscle. A relationship between coronary blood flow and tissue volume was observed. It was found to be independent of vasomotor tone. Vasodilation was found to increase available exchanging capillary surface at a constant perfusion pressure.
Chronic one-kidney hypertension in rabbits. II. Evidence for a new factor.
Authors: Skeggs L T , Kahn J R , Levine M , Dorer F E , Lentz K E
Published: June 2012

The arterial pressure of rabbits with chronic one-kidney hypertension can be lowered to normotensive levels by direct immunization with preparations made from the cortex of hog kidneys. Hypertensive rabbits that are immunized with large amounts of renin may develop high plasma antirenin titers without affecting their blood pressure. Removal of renin by chromatography on columns of immobilized antirenin yields preparations with little or no renin. Such preparations may be effective in lowering blood pressure although they do not elicit the formation of plasma antirenin and the rabbits remain sensitive to challenging doses of rabbit renin. The evidence suggests that an unknown substance is responsible for the development of a cross-reacting antibody that neutralizes an unknown factor that is essential for the maintence of an elevated blood pressure level in rabbits with chronic one-kidney hypertension.
Hormonal and nutritional substrate control of cardiac lysosomal enzyme activities.
Authors: Wildenthal K
Published: June 2012

Prolonged starvation is known to induce significant alterations in several cardiac lysosomal enzymes, particularly the acid proteinase cathepsin D. To determine what specific factors might mediate these changes, fetal mouse hearts in organ culture were maintained in media designed to simulate selected hormonal or nutritional substrate changes that accompany starvation. Reduced concentrations of glucose caused an increase in the activity of beta-acetylglucosaminidase but had no effect on cathepsin D or acid phosphatase activites (i.e., effects opposite from those of starvation). Also, high concentrations of free fatty acid, acetoacetate, and beta-OH-butyrate induced an increase in cathepsin D (+18%) and a simultaneous decrease in glucosaminidase (-19%), with little change in acid phosphatase. Furthermore, glucagon had no effect on any of the enzymes, whereas growth hormone caused a small (6%) increase in cathepsin D activity. In addition, insulin deprivation caused significant increases (7-25%) in the activities of all three enzymes. Insulin deprivation and excess ketones, but not the other interventions, increased the proportion of enzyme activity which was nonsedimentable. These results suggest the possibility that lysosomal alterations during starvation may be related in part to prolonged insulin deficiency and exposure to high concentrations of ketones and free fatty acids.
Vasomotor control of capillary transit time heterogeneity in the canine coronary circulation.
Authors: Rose C P , Goresky C A
Published: June 2012

A set of indicator-dilution studies of the coronary circulation of the intact functioning heart was carried out in the dog to provide a data base for defining the effect of changes in vasomotor control on the exchange of materials across the myocardial capillaries. The reference substance used was 125I-labeled albumin; the diffusible substance used was 14C-labeled sucrose. Model analyses of the data were carried out. In previous models of the capillary exchange in the coronary circulation, it had been assumed that a single capillary transit time is representative of the whole. The data acquired here indicate that there is a very large heterogeneity of capillary transit times in the intact heart, and that the single transit time model is approximately true only when the resistance vessels are maximally dilated. The present pattern of findings is explained best by a model of the coronary microcirculation based on capillary-large vessel units with a variable heterogeneity of flow or capillary lengths, hence of transit times. We conclude that a major determinant of the extraction of each diffusible substance, on a microscopic level, is the distribution of capillary transit times.
Effect of steric restriction on the intracortical distribution of microspheres in the dog kidney.
Authors: Morkrid L , Ofstad J , Willassen Y
Published: June 2012

The effect on the intracortical distribution of microspheres and radioactivity caused by steric hindrance of the free movement of spheres into afferent arterioles are described by two mathematical models. The results are compared with corresponding experimental data obtained in six kidneys from normotensive dogs. The first model (A) assumes that spheres are distributed as blood flow, regardless of their size, except for those having diameters greater than that of an afferent arteriole and which do not enter this vessel. The second model (B) includes the Ferry correction. The experimental data show that the percent recovery of spheres with diameters of 20-25 mum was significantly greater in the outer cortex and significantly less in the juxtamedullary cortex than recovery of the smaller spheres, and that the distribution of spheres with diameters of 10 mum to about 17 mum seems uninfluenced by the sphere size. The experimental results we have obtained fit best with model A. We found that according to both models steric restriction is a factor of major importance in relation to the intracortical distribution of spheres, and the analysis shows that the blood flow in the inner part of the renal cortex is grossly underestimated by the method of isotope labeled microspheres when diameters of 15 +/- 5 mum are used in the dog. Furthermore we found that dilation of the afferent arterioles will change the steric hindrance so that a redistribution of spheres and radioactivity may occur without any redistribution of blood flow. It is suggested that the results interpreted as redistribution of blood flow can be explained as due to altered steric hindrance alone, i.e., as a methodological artifact.
Localization of glucocorticoid uptake in normal and ischemic myocardial tissue of isolated perfused cat hearts.
Authors: Okuda M , Young K R , Lefer A M
Published: June 2012

We studied the uptake of labeled dexamethasone (3H-Dex) or methylprednisolone (3H-MP) in isolated perfused cat hearts during the first hour of acute myocardial ischemia. Considerable amounts of 3H-Dex and 3H-MP were taken up by the plasma membrane (F1) fraction in control, border zone, and ischemic myocardial tissue. Lesser amounts were incorporated into the remaining cell fractions. A gradient of glucocorticoid uptake was observed that decreased from control tissue to ischemic tissue in all subcellular fractions (i.e., F1 to F5). Accordingly, supernatant fraction (S) to particulate (P) ratios of labeled glucocorticoid uptake increased from control to ischemic tissue, indicating that myocardial cell damage resulted in a decrease in glucocorticoid-binding capacity in subcellular fractions obtained from ischemic tissue. The activity of 5'-nucleotidase (5'ND), a plasma membrane marker in myocardial cells, also decreased from normal to ischemic tissue. Furthermore, we found that uptake of 3H-MP and 3H-Dex was associated with the retention of 5'ND activity in F1 fractions of both border zone and ischemic tissue. Similar protection of plasma membrane integritg occurred in the supernatant fraction as determined by changes in S/P ratios of 5'ND activity. These data provide support for the concepts that (1) plasma membrane changes occur soon after acute myocardial ischemia, and (2) the mechanism by which glucocorticoids exert a protective effect in myocardial ischemia may be related to membrane stabilization.
The myocardial energetic active state. I. Oxygen consumption during tetanus of cat papillary muscle.
Authors: Cooper G
Published: June 2012

The potential role of active state maintenance as a determinant of myocardial oxygen consumption (MVO2) has not been defined. Right ventricular papillary muscles from 15 cats were studied in a polarographic myograph at 23 degrees C in a Krebs-Ringer solution containing 7.5 mM Ca2+ and 10 mM caffeine. MVO2 was determined for isometric tetani at Lmax of 1-5 seconds' duration. Increases in tetanus duration related linearly to increments in both active tension time (delta active tension) and MVO2. In order to examine the oxygen cost of active state maintenance not attributable to associated tension generation, both the same isometric and 2.5- to 10.0-second lightly preloaded isotonic tetani were produced in nine muscles. For each tetanus duration the contribution throughout the contraction of developed force (preload) to MVO2 could be subtracted from overall isotonic MV02. In the absence of the MVO2 associated with force development, the active state duration was related linearly to MVO2, with a mean active state MVO2 of 2.42 +/- 0.29 nl O2/mg dry muscle/sec of isotonic tetanus; this MVO2 is 68% of the value of 3.58 +/- 0.42 nl O2/mg dry muscle/sec that was obtained for isometric tetanus at Lmax. This study identifies active state maintenance as the major determinant of MVO2 during myocardial tetanus and, furthermore, suggests the possibility that alterations in ative state intensity and duration may be the biochemical mechanism by which other determinants of MVO2 act in a more physiological setting.