Rise In Systemic Arterial Pressure Research Articles

Abstract 267: Ablation of Sympathetic Neurons Projecting to Mesenteric Blood Vessels Attenuates Nicotine-Induced Rise in Systemic Arterial Pressure

Celiac ganglionectomy attenuates the increase in arterial pressure (AP) seen in the DOCA-salt model of hypertension; however, it is unknown which population of neurons in the celiac ganglion (CG) is responsible for this attenuation. Therefore, we ablated sympathetic post ganglionic neurons selectively innervating mesenteric blood vessels by applying a retrograde tracer, cholera toxin subunit b, conjugated to the neurotoxin saporin (CTB-SAP) on multiple, adjacent branches (~6mm) of mesenteric arteries and veins. Control animals received PBS instead of a CTB-SAP treatment. After 7-10 days rats were anesthetized, and fitted with a femoral catheter to record AP. Nicotine (200mM) was then applied to the surface of the surgically-exposed CG, which caused a significant increase in AP in control animals but not in CTB-SAP treated animals ( Table 1 ). Quantitative morphometry done on the CG revealed a significant reduction in the density of ganglionic neurons in CTB-SAP treated animals when compared to control animals ( Table 1 ). This study shows ablating CG neurons that innervate such a small portion of the mesenteric vasculature reduces the elevation of systemic AP induced by nicotine. Moreover, this study gives way for further investigations into how ablation of neurons innervating mesenteric arteries or veins can modulate AP.

Neurovascular complications of cocaine.

Use of cocaine in the USA, has reached epidemic proportions since 1983, when "crack" was introduced, its higher potency compared with cocaine HCl has been associated with a tremendous increase in the incidence of strokes. This study reports our experience with 55 cases of neurovascular events (25 ischemic and 30 hemorrhagic) related to cocaine use in 54 patients. Only 15 patients had other risk factors for stroke. Twenty six patients smoked "crack", 10 snorted cocaine and 12 injected it intravenously. Strokes occurred within 3 h of cocaine use in 15 patients with infarcts and 17 with hemorrhages. Ten infarcts occurred after an overnight binge. Of the hemorrhage group 9 were subarachnoid, 16 intracerebral (8 basal ganglia, 7 hemispheric and one brain stem) and 5 intraventricular. Computerized tomography (CT) showed an aneurysm of the anterior communicating artery, as well as one of the vein of Galen. Four aneurysms and 3 AVMs were identified on angiography. CT revealed 15 infarcts; it was normal in 7 patients with pure motor hemiparesis and in 3 with findings consistent with anterior spinal artery infarction. Several mechanisms may be responsible for the cerebrovascular complications. A sudden rise in systemic arterial pressure may cause hemorrhages, frequently in association with an underlying aneurysm or AVM. Vasospasm, arteritis, myocardial infarction with cardiac arrhythmias and increased platelet aggregation may provoke infarcts.

Clonidine in the management of hypertensive crisis (author's transl)

Haemodynamic data were obtained by means of Swan-Ganz balloon catheters in eight patients during hypertensive crisis. After obtaining control values, 150 microgram clonidine in 10 ml isotonic sodium chloride was administered intravenously over ten minutes. During the hypertensive crisis there was a moderate rise in pulmonary artery and right ventricular pressures, in addition to a rise in systemic arterial pressure. In addition there was a lower than normal cardiac index, averaging 2.2 l/min.m2, a reduced stroke volume of 49.3 ml, a markedly elevated peripheral vascular resistance of 3584 dyn.s.cm-5, and an elevated cardiac work index of 5.08 kg.m/min.m2. After clonidine administration there was a significant fall in systolic, diastolic and mean femoral artery pressures (P less than 0.005), without any significant fall in pulmonary artery and right ventricular pressures. At the same time there was a further fall in cardiac index to an average of 1.85 l/min.m3, largely due to a reduced heart rate. Stroke volume fell slightly in only two patients. Peripheral vascular resistance did not fall significantly, while cardiac work index was significantly below the control value as late as four hours after clonidine administration.

A Preterm Infant Who Has Acute Respiratory Decompensation

A 4-day-old preterm male infant presents with respiratory failure requiring 100% oxygen on assisted ventilation. ### Prenatal History: ### Birth History and Presentation: The infant was delivered by the vaginal route in vertex presentation. He had initial poor respiratory effort, but responded to warming, stimulation, and blow-by oxygen. Apgar scores were 7 at 1 minute and 8 at 5 minutes. He continued to demonstrate increased work of breathing and was intubated in the delivery room. He was admitted to the neonatal intensive care unit (NICU) for prematurity and respiratory distress. His birthweight was 1,589 g, which was appropriate for gestational age. Thirty minutes after birth, the patient had worsening tachypnea and subcostal retractions; chest radiograph at this time demonstrated diffuse bilateral reticular granular densities and microatelectasis CXR 1 . Oxygen saturation in room air was 78%. When 100% oxygen was administered, the oxygen saturation increased to 92%. Arterial blood gas (ABG) revealed: What is the appropriate treatment of this infant at this time? On arrival to the NICU, the patient was intubated and placed on mechanical ventilation. An echocardiogram revealed normal cardiac structure and function. The blood lactate level was elevated at 225.2 mg/dL (25 mmol/L). Blood ammonia concentration also was elevated at 518 mmol/L. Ketones were noted in the urine. ### Vital Signs Were: ### Physical Examination

Characterization of acute reversible systemic hypertension in a model of heme protein-induced renal injury.

In the glycerol model of renal injury we describe an acute rise in systemic arterial pressure which is attended by a reduced vasodilatory response to acetylcholine in vivo; vasodilatory responses to verapamil, however, were not impaired. Neither arginine nor sodium nitroprusside diminished this rise in blood pressure; N(omega)-nitro-L-arginine methyl ester (L-NAME) elevated basal mean arterial pressure and markedly blunted the rise in mean arterial pressure following the administration of glycerol. Aortic rings from the glycerol-treated rat demonstrate an impaired vasodilatory response to acetylcholine, an effect not repaired by arginine; the vasodilatory responses to nitric oxide donors, sodium nitroprusside and SIN-1, were also impaired; 8-bromo-cGMP, at higher doses, evinced a vasodilatory response comparable to that observed in the control rings. This pattern of responses was not a nonspecific effect of aortic injury, since aortic rings treated with mercuric chloride, a potent oxidant, displayed an impaired vasodilatory response to acetylcholine but not to sodium nitroprusside. We conclude that in the glycerol model of heme protein-induced tissue injury, there is an acute elevation in mean arterial pressure attended by impaired endothelium-dependent vasodilatation in vitro and in vivo. We suggest that the acute scavenging of nitric oxide by heme proteins depletes the blood vessel wall of its endogenous vasodilator and permeation of heme proteins into the blood vessel wall may contribute to such sustained effects as observed in vitro.

Medullary inputs to nucleus accumbens neurons.

Extracellular single-unit recording experiments were done in alpha-chloralose-anesthetized, paralyzed, and artificially ventilated rats to investigate the effect of stimulation of the nucleus of the solitary tract (NTS) and the ventrolateral medulla (VLM) in the region of the A1 noradrenergic cell group on the activity of neurons in the nucleus accumbens (NA). In addition, the response of NA neurons to activation of the arterial baroreceptors was investigated. Electrical or glutamate (Glu) stimulation of the ipsilateral NTS excited 47 of 99 (48%) and inhibited 10 of 99 (10%) of the units tested in the NA. Similarly, electrical or Glu stimulation of the ipsilateral VLM excited 24 of 97 (24.7%) or inhibited 7 of 97 (7.2%) of the units tested. Approximately 22% (17 of 77) of these units responded to stimulation of both the NTS and VLM. Simultaneous stimulation of both the NTS and VLM potentiated the response of the NA neuron tested. CoCl2 injection into the ipsilateral NTS did not alter the response of NA neurons to stimulation of the VLM. Similarly, CoCl2 injections into the ipsilateral VLM did not alter the response of NA neurons to NTS stimulation. The discharge rate of some of the units (6 of 49) that were activated by both NTS and VLM was also increased during the activation of arterial baroreceptors by the acute rise in systemic arterial pressure to phenylephrine injection. Units that responded to stimulation of the NTS and VLM and to baroreceptor activation were located in the shell region of the NA. These data indicate that afferent inputs from the NTS and VLM converge onto NA neurons and suggest that visceral and cardiovascular afferent inputs may influence the output of neurons in the shell region of the NA.

Mechanisms of centrally administered ET-1-induced increases in systemic arterial pressure and AVP secretion.

Endothelins (ET) within the central nervous system (CNS) alter systemic cardiovascular responses and arginine vasopressin (AVP) secretion. These experiments were designed to ascertain whether the rise in systemic arterial pressure after central administration of ET-1 is mediated by enhancing sympathetic outflow and/or circulating AVP. In Long-Evans (LE/LE) rats, intracerebroventricular injection of 1-10 pmol ET-1 dose dependently increased mean arterial pressure (MAP). Peak response occurred 7-12 min after ET-1 and was inhibited by ETA receptor antagonism. Systemic vasopressin (V1) receptor blockade did not inhibit the pressor response, and rats with central diabetes insipidus (DI/DI) displayed an identical rise in MAP. Ganglionic blockade prevented ET-1-induced hemodynamic effects. Peak plasma AVP levels occurred 60 min after ET-1, as the pressor response began to wane. In sinoaortic-denervated LE/LE rats, ET-1 elicited a 10-fold increase in AVP secretion that coincided with the hemodynamic changes and was blocked by BQ-123. Thus ET-1 via ETA receptors within the CNS induced a concentration-dependent increase in systemic arterial pressure mediated by enhanced sympathetic outflow but not by circulating AVP. Reflex baroreceptor activation attenuated AVP release.

Alteration of testicular microvascular pressures during venous pressure elevation.

We have addressed the hypothesis that varicocele-related infertility is caused in part by a pressure-induced disturbance of testicular convective transport that upsets the testicular hormonal environment and thus impairs spermatogenesis. The left testis of the hamster [pentobarbital sodium (Nembutal), 70 mg/kg ip] was prepared for microcirculatory observations. Testicular venous pressure was acutely elevated by ligating collateral routes of venous outflow and partially occluding, via a snare, the main venous outflow distal to the pampiniform plexus. Simultaneous direct pressure measurements (servo-null method) were made to monitor venous pressure elevation and quantify resulting pressure and diameter changes in the arterial feed to the testis and in postcapillary venules. The data show that over 90% of the venous pressure elevation (VPE) was transmitted to the postcapillary venules. VPE affected intravascular pressures throughout the testis microvasculature; on average, capsular artery pressure increased by 83% of the VPE, although part of this increase was due to a rise in systemic arterial pressure. Vasoconstriction helped to buffer the pressure rise in the capsular artery, probably at the expense of flow amplitude. Yet the vasoconstriction was ineffective in preventing a rise in exchange vessel pressure. These data suggest that microvascular fluid exchange may be dramatically altered in varicocele, upsetting the hormonal and paracrine environment of the testis, and hence, impairing physiological regulation of gametogenesis.

Regional blood flow in brain and peripheral tissues during acute experimental arterial subdural bleeding.

The effects of a large intracranial arterial subdural bleeding on regional blood flow in the brain (rCBF) and in other body organs were studied, using a porcine model. The bleeding was produced by leading blood through a catheter from the abdominal aorta via an electronic drop recorder into the subdural compartment (SDC) over the left cerebral hemisphere. Pressures in the right lateral cerebral ventricle and in the cisterna magna were recorded along with 15 other vital parameters. Measurements of rCBF were carried out using radioactive microspheres 1) before the start of bleeding, 2) during the early bleeding phase, and 3) during the late bleeding phase. When the bleeding was initiated, the intracranial pressures rose within one minute to a level approximately 40 mmHg below the systemic arterial pressure, whilst the latter usually decreased 30-40 mmHg. In the subsequent early bleeding phase the cerebral perfusion pressure and the bleeding pressure fluctuated at a level of approximately 40 mmHg for several minutes. In the late bleeding phase, the perfusion pressure decreased maximally, even when a Cushing reaction was activated. During the early bleeding phase the changes in rCBF varied between the cerebral regions. However, the mean flow remained largely constant in the presence of a decreasing cerebrovascular resistance, indicating that autoregulation of CBF was intact. Concomitantly, cardiac output and heart rate decreased, whilst regional blood flow in extracerebral organs tended to increase, possibly due to an intracranial effect on the autonomic nervous system. In the late bleeding phase, rCBF was critically reduced in all regions, in spite of a marked rise in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of monoclonal anti-ANP antibodies on the acute functional adaptation to unilateral nephrectomy

The role of endogenous atrial natriuretic peptide (ANP) in the immediate response of sodium excretion to unilateral nephrectomy (UNX) was investigated in anesthetized euvolemic rats through measurement of UNX-induced change in plasma ANP concentration and the response of the remaining kidney to UNX following administration of monoclonal anti-ANP antibodies. The circulating ANP levels almost tripled (from 23 +/- 4 to 66 +/- 13 fmol/ml, P < 0.01) within two minutes after UNX, whereas no change resulted from sham intervention. In the control group receiving vehicle injection, UNX resulted in a twofold increase in urinary sodium excretion (from 1.39 +/- 0.25 to 2.88 +/- 0.28 mumol/min, P < 0.01) related to a decrease in the fractional reabsorption of sodium at both proximal and distal sites (estimated from fractional excretion of lithium). Urinary excretion of cyclic guanosine 3'-5'-monophosphate (cGMP) increased as well, but glomerular filtration rate did not change. In addition, UNX was associated with a short-lived (< 20 min) rise in systemic arterial pressure and a transient fall in right atrial pressure. Administration of monoclonal anti-ANP antibodies totally prevented the UNX-associated natriuresis by blunting both proximal and distal tubular reabsorption of sodium, and suppressed the rise in urinary cGMP excretion following UNX. The duration of the post-UNX increase in arterial pressure was longer when compared to values observed in controls. These observations indicate that ANP release is stimulated after uninephrectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on supratentorial subdural bleeding using a porcine model.

A porcine model for an acute lethal arterial subdural bleeding in man is presented. Blood from the abdominal aorta was led via an electronic drop recorder into a collapsed intracranial subdural rubber balloon. Systemic arterial pressure (SAP), two intracranial pressures and 6 other vital parameters were monitored continuously in spontaneously breathing (n = 4) and mechanically ventilated (n = 4) pigs. In both animal groups bleeding caused an immediate rise in intracranial pressures (ICP) with transtentorial pressure gradients developing. As a result the cerebral perfusion pressures (CPP) decreased progressively, leading to an isoelectric EEG. In spontaneously breathing animals, the pressure changes resulted in apnoea within 2-4 minutes, irregularities in heart rhythm and in a marked rise in SAP (the Cushing reaction). A final collapse of all pressures occurred after 222 +/- 68 sec at a mean bleeding volume of 10.3 +/- 1.9 ml. In contrast, in mechanically ventilated animals, the course of bleeding was less dramatic. No change in cardiac rhythm or rise in SAP appeared despite a larger mean bleeding volume (12.0 +/- 1.6 ml). Instead, SAP slowly fell, reaching a level of approximately 40 mm Hg within 1 hour, while CPP concomitantly decreased from 120 mm Hg to 15 mm Hg. The findings in this and in a parallel study are explained in terms of the intracranial volume tolerance concept (Zwetnow et al. 1986). The beneficial effect of assisted ventilation on the course of subdural bleeding is multifactorial, involving both metabolic and mechanical mechanisms.

Predisposition to essential hypertension and the development of diabetic nephropathy.

Only a subset of insulin-dependent diabetic patients are at risk of developing nephropathy. Prospective studies of uncomplicated insulin-dependent diabetic cohorts have shown that a rise in systemic arterial pressure is a concomitant feature of the progression to early nephropathy. The development of hypertension is an integral feature of established nephropathy in diabetes, and its amelioration retards the progression of disease and may improve overall mortality. Family studies have suggested that nondiabetic parents of insulin-dependent diabetic patients with nephropathy have a greater prevalence of hypertension, and in certain groups of non-insulin dependent patients, it has been found that the blood pressure before the onset of diabetes correlates with the development of nephropathy after the onset of diabetes. These results indicate that a propensity to hypertension may be part of the genetic predisposition to nephropathy. This contention is further supported by the finding that a raised erythrocyte sodium-lithium countertransport, a biochemical marker of hypertension and cardiovascular disease whose activity is largely genetically determined, occurs with greater frequency in proteinuric diabetic patients and their nondiabetic parents than in those diabetic patients without nephropathy and their parents. Recent family studies have also shown that a family history of cardiovascular disease significantly increases the risk of nephropathy by up to three-fold in insulin-dependent diabetes. It is suggested that the cardiorenal complications of diabetes mellitus may be linked to reduced insulin sensitivity, which itself is associated with hypertension, raised sodium-lithium countertransport rates, and cardiovascular disease.

Importance of prostaglandins in hypertension during reduced uteroplacental perfusion pressure.

Uteroplacental ischemia causes hypertension in various species but the mechanisms involved are not known. These studies were designed to test the hypothesis that the systemic hypertension that occurs during reduced uteroplacental perfusion pressure is mediated by the prostaglandin system. Trained chronically instrumented pregnant dogs in the last third of gestation were studied. When uterine perfusion pressure was reduced to 60 mmHg for 60 min using an inflatable aortic occluder placed distal to the renal but proximal to the uterine and ovarian arteries, systemic arterial pressure increased from 95 +/- 5 to 110 +/- 7 mmHg. On another day in the same animals, the prostaglandin system was blocked with meclofenamate. Subsequent reduction of uterine arterial pressure caused no significant change in systemic pressure, from 96 +/- 4 to 99 +/- 6 mmHg, suggesting an important role for the prostaglandin system in mediating the normal response. In additional experiments, the thromboxane receptor antagonist SQ 29,548 was given. Arterial pressure averaged 94 +/- 5 mmHg after administration of SQ 29,548 and did not change significantly when uterine perfusion pressure was reduced during SQ 29,548. These data suggest that at least one component of the prostaglandin system, thromboxane, contributes to the rise in systemic arterial pressure during reduced uteroplacental perfusion pressure.

Effect of isometric exercise on cardiac performance and mitral regurgitation in patients with severe congestive heart failure

Left ventricular performance was studied during isometric exercise in 17 patients with severe congestive heart failure, combining invasive hemodynamic and echo-Doppler techniques. Isometric exercise at 30% of maximum resulted in a decrease in stroke volume index (27.4 ± 7.1 to 22.7 ± 7.4 ml/m 2), with a significant increase in heart rate from 81 ± 10 to 92 ± 14 beats/min and in systemic vascular resistance from 1827 ± 527 to 2372 ± 737 dyne · sec · cm −5. A significant rise in pulmonary capillary wedge pressure (18 ± 9 to 31 ± 10 mm Hg) was associated with a marked increase in mitral regurgitant volume (14 ± 11 to 27 ± 15 ml), calculated as the difference between total stroke volume obtained by two-dimensional echocardiography and forward stroke volume measured by pulsed Doppler at the aortic anulus. During isometric exercise, left ventricular end-diastolic and end-systolic volumes did not change markedly, but the total stroke volume tended to increase from 62 ± 13 to 67 ± 13 ml. The increase in mitral regurgitant volume induced by isometric exercise was correlated with the fall in forward stroke volume ( r = 0.7, p < 0.01). Thus a rise in systemic arterial pressure induced by isometric exercise is associated with a decrease in cardiac performance attributable to redistribution of total left ventricular output with an increase in mitral regurgitation and a simultaneous decrease in forward cardiac output.

Genetic co-segregation of renal haemodynamics and blood pressure in the spontaneously hypertensive rat

1. To determine the relevance of renal circulatory abnormalities found in the immature spontaneously hypertensive rat (SHR) to the genetic hypertensive process, glomerular filtration rate and renal blood flow were measured in conscious F2 rats, derived from cross-breeding SHR and normotensive Wistar-Kyoto rats (WKY), at 4, 11 and 16 weeks of age by determining the renal clearances of 51Cr-ethylenediaminetetra-acetate and 125I-hippuran respectively. Plasma renin activity was measured at 11 and 16 weeks of age. 2. Mean arterial pressure, glomerular filtration rate and renal blood flow increased between 4 and 11 weeks of age. Between 11 and 16 weeks the mean glomerular filtration rate and renal blood flow did not alter, although the mean arterial pressure rose significantly. At 11 weeks of age, during the developmental phase of hypertension, a significant negative correlation between mean arterial pressure and both glomerular filtration rate and renal blood flow was noted. However, by 16 weeks when the manifestations of genetic hypertension were more fully expressed, no correlation between mean arterial pressure and renal blood flow or glomerular filtration rate was observed. Plasma renin activity was negatively correlated with both glomerular filtration rate and renal blood flow, but the relationship was stronger at 11 than at 16 weeks of age. 3. These results suggest that the reduction in renal blood flow and glomerular filtration rate, found in immature SHR, is genetically linked to the hypertension and may be of primary pathogenetic importance. It is proposed that the increased renal vascular resistance in these young animals stimulates the rise of systemic arterial pressure which returns renal blood flow and glomerular filtration rate to normal.

Cardiovascular consequences of hypercalcemia during activity in two species of amphibian

AbstractExercise induced both a significant acidosis and hypercalcemia, measured as either total or ionic calcium in two species of amphibian, Bufo marinus and Rana catesbeiana. Hypercarbia induced a significant acidosis in both species but a significant hypercalcemia only in Bufo. Induction of hypercalcemia by infusion of Ca to concentrations equal to or greater than induced by exercise and hypercarbia had no significant effects in either species on mean arterial pressure, maximal rate of rise of systemic arterial pressure, blood flow rate, heart rate, pulse volume, or peripheral resistance during exercise. The ratio of ionic to total calcium was not significantly altered within a species by an experimental protocol. These data indicate that there are no discernible cardiovascular consequences during exercise of hypercalcemia induced by exercise or hypercarbia.

Ambulatory pulmonary arterial pressures in humans: relationship to arterial pressure and hormones.

Six healthy volunteers were studied by use of a continuous ambulatory recording technique to document the normal range and variability of pulmonary artery pressure (PAP) and to examine its relationship to systemic arterial pressure (SAP) both at rest and during standardized interventions. Vasoactive hormone levels were measured at frequent intervals. Over 8-10 h of study the mean PAP was 15.7/6.3 mmHg. Parallel changes in PAP and SAP were observed at rest and during exercise and eating. On the contrary, PAP rose and SAP fell with hypoxia, whereas smoking was associated with a rise in SAP but no change in PAP. Sympathetic nervous system activity, as gauged by plasma norepinephrine levels, may have contributed to pressure and heart rate changes during exercise and smoking, but activity of the renin-angiotensin system was not altered by any of the maneuvers. These results provide base-line information on the level of PAP and its variability in healthy volunteers under standardized conditions. Pressures within the systemic and pulmonary circuits change in parallel under some circumstances but move in opposite directions under other conditions.

Vasomotor center controls of the hepatic circulation during blood pressure oscillation in rabbits.

Changes in hepatic hemodynamics during blood pressure oscillations caused by the side pressure exertion procedure (SPEP) were studied in anesthetized rabbits. The brain was excluded from systemic circulation except for one of the common carotids, which was compressed with stepwise elevated pressure. In normovolemia, the hepatic arterial flow (HAF) increased as the systemic arterial pressure (SAP) rose up to 140 mmHg, and then decreased as SAP rose further. With the rise of SAP, the portal venous flow (PVF) initially rose slightly, followed by a nearly constant decrease. Hemorrhaging influenced slightly the changes of HAF and PVF with the SAP rise. After volume loading, SAP and PVF markedly increased but HAF changed little. However, the initial increase in HAF with the SAP rise was markedly depressed by volume loading. PVF conspicuously decreased without initial increase with the rise in SAP. The hepatic vascular bed has a mechanism that prevents expected decrease of blood flow after hemorrhaging and during neurogenic hypertension. The interaction among HAF, PVF, and PVP may be involved in this mechanism.

Effects of acute versus chronic deletion of arterial baroreceptor input on the cardiovascular responses to exercise in the rabbit.

These experiments were designed to confirm that at the onset of treadmill exercise in rabbits the tonic reflex depressor effects of input to the central nervous system from arterial baroreceptors is abolished, thus contributing to the rise of systemic arterial pressure (SAP) and heart rate (HR). An inflatable cuff was placed around one common carotid artery after the remaining arterial baroreceptors had been surgically denervated. Transient inflation of the cuff caused reflex rises of SAP and HR, which were much reduced during the first minute of exercise. Deflation of the cuff caused a brisk fall of HR, which was completely abolished by exercise. A snare was placed around one carotid sinus nerve after the remaining arterial baroreceptors had been surgically denervated. Where the snare was tightened all arterial baroreceptor reflexes were immediately and permanently abolished. This allowed the reflex effects of baroreceptor input to be calculated by difference. The magnitude of these calculated effects, at rest and during exercise, diminished according to how long after barodenervation the observations were made. We conclude from the above experiments that the resting tonic reflex depression of SAP and HR caused by baroreceptor input is much reduced, rather than completely abolished, at the onset of exercise. We also conclude, from the effects of partial surgical barodenervation, and of unloading the carotid baroreceptors prior to exercise by inflating the carotid cuff, that resting input from the arterial baroreceptors must be near zero before the cardiovascular response to exercise is grossly altered.

Direct observations of responses of mesenteric microcirculation of the rat to circulating noradrenaline.

The responses of mesenteric microcirculation of the rat to circulating noradrenaline were studied by in vivo microscopy, using a photo-electric device placed on a television monitor to measure changes in diameter of individual vessels. Blood flow was measured in the anterior mesenteric artery with an electromagnetic flow transducer, mesenteric vascular conductance was computed on-line from mesenteric artery flow and arterial pressure. I.V. injection of noradrenaline induced a decrease in diameter of arterioles (less than 30 microns) which began simultaneously with the rise in arterial pressure and averaged 15% at 15-20 s. By contrast small and principal arteries (30-40 microns and 80-350 microns respectively) generally showed a diameter increase which averaged 10% and began at the peak of the pressor response. Venules and veins (12-560 microns) showed a diameter decrease which averaged 12-15% at 25-30 s. Meanwhile mesenteric vascular conductance fell by 65-75% in 10 s and rose to 30-50% above control in 25-30 s. The diameter increases of small and principal arteries were not reflex dilator responses initiated by the rise in systemic arterial pressure, nor due to beta-adrenoreceptor stimulation. However, local application of phentolamine abolished responses of all sections of the vascular tree indicating that they all depended on activation of alpha-adrenoreceptors. During I.V. infusion of noradrenaline small arteries showed a maintained increase in diameter which began at the peak of the pressor response, while arterioles initially decreased in diameter but then relaxed, often attaining resting diameter before infusion ceased. Meanwhile mesenteric flow and conductance decreased transiently, but then returned to near control levels, i.e. 'autoregulatory escape' occurred. It is argued that noradrenaline induced alpha-mediated contraction of all sections of the vascular tree; the tendency of arteries to constrict was counteracted by the rise in intravascular pressure caused by arteriolar constriction, active constriction of venous vessels may have been augmented by passive collapse secondary to arteriolar constriction. The secondary relaxation of arterial vessels reflects an inherent property of their smooth muscle to relax from the constrictor influence of noradrenaline and is more marked in proximal than distal vessels. It is proposed that the initial decrease in mesenteric vascular conductance in response to circulating noradrenaline may be attributed to active constriction of distal arterioles and the secondary increase in conductance ('escape') to secondary relaxation of more proximal arterial vessels.