Baroreceptor Mechanisms Research Articles

Thyroid hormones and renin secretion

Circulating angiotensin is produced by the action of renin from the kidneys on circulating angiotensinogen. There are other renin-angiotensin systems in various organs in the body, and recent observations raise the intriguing possibility that angiotensin II is produced by a totally intracellular pathway in the juxtaglomerular cells, the gonadotrops of the anterior pituitary, neurons in the brain, salivary duct cells, and neuroblastoma cells. Circulating angiotensin II levels depend in large part on the plasma concentration of angiotensinogen, which is hormonally regulated, and on the rate of renin secretion. Renin secretion is regulated by an intrarenal baroreceptor mechanism, a macula densa mechanism, angiotensin II, vasopressin, and the sympathetic nervous system. The increase in renin secretion produced by sympathetic discharge is mediated for the most part by β-adrenergic receptors, which are probably located on the juxtaglomerular cells. Hyperthyroidism would be expected to be associated with increased renin secretion in view of the increased β-adrenergic activity in this condition, and hypothyroidism would be associated with decreased plasma renin activity due to decreased β-adrenergic activity. Our recent research on serotonin-mediated increases in renin secretion that depend on the integrity of the dorsal raphe nucleus and the mediobasal hypothalamus has led us to investigate the effect of the pituitary on the renin response to p-chloroamphetamine. The response is potentiated immediately after hypophysectomy, but 22 days after the operation, it is abolished. This slowly developing decrease in responsiveness may be due to decreased thyroid function.

Prostaglandins and renin release: the effect of PGI2, PGE2, and 13,14-dihydro PGE2 on the baroreceptor mechanism of renin release in the dog.

We compared the ability of the vasodilator prostaglandins PGI2, PGE2, and 13,14-dihydro PGE2 to release renin when infused into the denervated, nonfiltering canine kidney in vivo. Papaverine was used as a nonprostaglandin vasodilator. All the prostaglandins tested were capable of stimulating renin secretion, with the scale of potency being 13,14-dihydro PGE2 greater than PGI2 greater than PGE2; papaverine had no effect on renin secretion. These results indicate that both PGE2 and PGI2 can stimulate renin secretion but that vasodilation per se is not a stimulus. 13,14-Dihydro PGE2 was included because it is a poorer substrate than PGE2, both for transport into cells and catabolism to inactive products, but has comparable potency to PGE2 when tested in systems with limited ability to catabolize PGE2. The fact that 13,14-dihydro PGE2 was the most potent prostaglandin tested suggests that the effects of PGE2 in our system are reduced by the kidneys' recognized ability to extract and catabolize PGE2. Since PGI2 is less avidly metabolized than PGE2 by the kidney, the differences in observed potency between PGE2 and PGI2 could be largely the result of differences in renal catabolism of the two prostaglandins rather than differences in intrinsic potency. Therefore, both PGE2 and PGI2 are candidates for the endogenous prostaglandin responsible for stimulating renin secretion.

INFLUENCE OF THE INTRARENAL BARORECEPTOR ON RENIN RELEASE DURING ACUTE RESPIRATORY ACIDOSIS IN DOG

The role of the renal vascular baroreceptor mechanism in the renin response elicited by acute respiratory acidosis was studied in 8 chloralose anesthetized dogs. Ventilation with 8% CO2 in air for 10 minutes (constant minute ventilation) resulted in a significant increase (P <0.01) in plasma renin activity (PRA) with a small, but insignificant, decrease in mean arterial pressure and increase in renal blood flow. The smooth muscle relaxant, papaverine, was infused into the renal artery (2 mg/min) to produced renal vasodilation and thus inhibit the renal vascular receptor for renin release. During intrarenal papaverine, the renin response to 8% CO2 inhalation was attenuated (P < 0.05) even though blood pressure fell (P < 0.01) by an average of 21 mmHg. The data indicated that the renin response during acute respiratory acidosis is papaverine sensitive and is mediated in part by the renal vascular baroreceptor mechanism.

The prostaglandin system. A role in canine baroreceptor control of renin release.

SUMMARY We used the nonfiltering kidney model with contralateral nephrectomy to investigate the site where prostaglandins influence renin release. Adrenergic influences on renin release were excluded by renal denervation, bilateral adrenalectomy, and a continuous propranolol infusion. In this model, reduction of renal perfusion pressure by 50% increased renal venous renin activity from 3.10 ± 0.66 to 13.14 ± 3.8 ng of angiotensin I/ml per hour within 10 minutes (P < 0.05). This increase in renin activity was abolished by pretreatment with indomethacin, 8 mg/kg, but not by the sodium carbonate buffer in which indomethacin was dissolved. Infusion of arachidonic acid into the artery of the nonfiltering kidney at a rate of 10 ' g/kg per minute for 20 minutes also increased the renal venous renin activity from a baseline of 2.35 ± 0.37 to 5.45 ± 2.45 ng of angiotensin I/ml per hour by the end of the infusion. This effect of arachidonic acid was blocked by indomethacin. A fatty acid, 11,14,17-eicosatrienoic acid, which is not a substrate for cyclooxygenase, had no effect on renin release in this model. These data indicate that the prostaglandin system can affect the renal baroreceptor mechanism for renin release. Stimulation of prostaglandin synthesis by providing arachidonic acid increased renin secretion, and inhibition of cyclooxygenase abolished the ability of the renal baroreceptor to respond to a reduced perfusion pressure with renin release. Furthermore, this interaction is probably due to products of the renal cortical cyclooxygenase since transport of prostaglandins from the medulla to the cortex in tubular fluid cannot occur in the nonfiltering kidney.

Changes in plasma catecholamines and dopamine beta-hydroxylase after corrective surgery for coarctation of the aorta.

In six patients within 12 hours of surgical correction of aortic coarctation there was a 750% increase in plasma noradrenaline concentrations accompanied by an increase in systolic and diastolic blood pressures. The magnitude of the postoperative increase in noradrenaline concentrations was related to the preoperative level of the pressure gradient across the coarctation. Six months after operation plasma noradrenaline concentrations were still significantly elevated. In nine patients who underwent other types of major surgery there was a small increase in plasma noradrenaline concentrations and a return to levels within the normal range within 24 hours. Various explanations for the rise in plasma noradrenaline concentrations are considered. In particular the possibility is raised that after surgical correction of aortic coarctation the increased levels indicate a marked increase in sympathetic nervous system activity; this may be mediated by baroreceptor mechanisms and may persist for up to six months after surgery.

Plasma renin levels and systemic haemodynamics in essential hypertension.

1. Plasma renin concentration, intra-arterial pressure, cardiac output and total peripheral resistance have been studied in 50 patients with essential hypertension and normal renal function. 2. Total peripheral resistance and plasma renin were negatively correlated (r = -0-45), indicating that 'high-renin' essential hypertension is not necessarily associated with arteriolar vasoconstriction. 3. The inverse relation between mean arterial pressure and plasma renin (r = -0-46) suggests a role for the renal baroreceptor mechanism in the suppression of renin in 'low-renin' hypertension. 4. Cardiac output was positively related to plasma renin concentration (r = +0-42). 5. Multiple regression analysis indicates that the described relationships were independent of age.

Renin stimulation by isoproterenol and theophylline in the isolated perfused kidney

The intrarenal mechanisms of renin release were studied in the isolated perfused rabbit kidney during stimulation by isoproterenol, 0.01 mug/kg per min, and by theophylline, 0.87 mg/kg per min. In the absence of urinary flow during the early stages of perfusion, isoproterenol caused a 17% increase of renal vein serum renin concentration (RVSRC) (P less than 0.001) without changing renal blood flow, renal vascular resistance, or serum potassium. dl-Propranolol, 2.0 mg/kg per min. abolished this isoproterenol-induced renin release. A moderate reduction in perfusion pressure prior to the infusion of isoproterenol resulted in a marked additional stimulation of renin release. Studies during and following ureteral occlusion demonstrated that theophylline stimulates renin release by decreasing renal vascular resistance, whereas the concomitant increase in sodium transport to the macula densa exerted an opposite effect. dl-Propranolol did not affect theophylline-induced renin secretion. It is concluded that single exogenous stimuli may activate more than one intrarenal mechanism simultaneously. Isoproterenol has a direct renin-stimulatory effect on intrarenal beta-adrenergic receptors that may be reinforced by baroreceptor stimulation. Theophylline stimulates renin via a baroreceptor mechanism, with simultaneous renin suppression via a sodium-macula densa effect.

Changes in renal hemodynamics and renin release caused by increased plasma oncotic pressure

The effect of increased plasma oncotic pressure on renal blood flow (RBF), glomerular filtration rate (GFR), electrolyte excretion, and renin secretion rate (RSR) was studied in dogs anesthetized with sodium pentobarbital. Renal artery infusions of hyperoncotic dextran or human serum albumin raised renal venous colloid osmotic pressure an average of 7.3 and 10.1 mmHg, respectively, and caused small but consistent increases in RBF, large increases in RSR, marked decreases in urine flow rate and electrolyte excretion, with either no change or small decreases in GFR, and no change in renal artery pressure. Renal vasodilation was confined primarily to afferent arterioles and was not measureable until approximately 45 s after the start of infusions. The renal responses to increased plasma oncotic pressure appeared to be an autoregulatory phenomenon, consistent with a tubular mechanism dependent on an altered distal tubular fluid flow and/or composition. The increased renin release during increased plasma oncotic pressure is not compatible with a renal baroreceptor mechanism that responds to decreases in afferent arteriolar pressure because calculated glomerular pressure increased during albumin and dextran infusions.

Studies on the centrally mediated hypotensive activity of guanabenz

Prior studies demonstrated that guanabenz reduces systemic blood pressure by inhibiting central sympathetic outflow as well as by adrenergic neuron blockade. Potential mechanisms responsible for the reduction of efferent sympathetic activity were examined in the present series. Guanabenz failed to modify carotid sinus nerve activity in a perfused sinus preparation. It reduced sympathetic outflow, heart rate and blood pressure in debuffered cats indicating that its actions are not mediated primarily by baroreceptor mechanisms. α-Adrenergic blockade greatly attenuated the response suggesting that the central sympathoinhibitory effect of guanabenz results from α-adrenergic receptor activation. Only a high dose of the compound attenuated the increase in sympathetic nerve activity produced by stimulation of the posterior hypothalamus. These experiments lead to the overall conclusion that guanabenz acts primarily at sites which regulate the basal of sympathetic outflow.

Distribution of cardiac output in dogs during intravenous infusion of betahistine.

Cardiac output (CO), arterial blood pressure (ABP), heart rate (HR), blood gases and blood flow (BF) to the brain, heart, kidney and skeletal muscles and other cephalic tissues in five dogs were studied before and at 30 minutes of betahistine infusion (0.12 to 0.2 mg per minute per kilogram). The particle distribution method using radioactive labeled 141Ce (15 mu) and 85Sr (15 mu) microspheres was utilized to quantitate and assess BF and CO. In the five dogs, the increase in CO averaged 20.8%, ABP remained constant, and HR increased in all but one exception where it decreased slightly concomitant with a decrease in Paco2. Brain BF increased (+ 29.6%) in the dogs whose Paco2 reamined constant. The BF increased to the heart (25.4%) and skeletal muslce (80%), while BF to the kidney and other tissues did not change. The change in HR appears to account for the change in CO. The dilating effect of betahistine on blood vessels, in the skeletal muscle, brain and heart could reduce peripheral resistance and decreace ABP. Thus, the increase in HR may be mediated through baroreceptor mechanisms rather than by a direct effect of betahistine. In addition, a decrease in Paco2, is more effective for decreasing cerebral BF than betahistine is for increasing blood flow.

Control of renin secretion in the dog. Effects of furosemide on the vascular and macula densa receptors.

Experiments were undertaken to investigate further the effect of furosemide on renin secretion in the anesthetized dog. To separate the effects of the macula densa and the baroreceptor mechanisms, experiments were conducted in kidneys made nonfiltering by combining 2.5 hours of renal ischemia with ureteral ligation. Furosemide, in a dose of 5 mg/kg, increased renin secretion and decreased renal resistance in dogs with a nonfiltering kidney. Prior dilation of the nonfiltering kidney with either acetylcholine or papaverine prevented changes in both resistance and renin secretion. However, following dilation of the intact filtering kidney with acetylcholine, furosemide caused an increase in renin secretion. Infusion of d,l-propranolol decreased renin secretion in both the filtering and the nonfiltering kidneys. Following propranolol treatment, furosemide increased renin secretion in the filtering kidney but had no effect on renal resistance. These experiments indicate that furosemide stimulates renin secretion by both the macula densa and the baroreceptor mechanisms. The data suggest that stimulation of the sympathetic nervous system may alter renin secretion by modulating the renal baroreceptor, but sympathetic innervation does not appear to be involved in the macula densa mechanism.

Reflex heart rate control via specific aortic nerve afferents in the rabbit.

Reflex bradycardia was elicited in rabbits via repetitive electrical stimulation of the central end of the sectioned left aortic nerve. Supramaximal stimulation produced a 16.9 plus or minus 1.3% (SE) increase in the R-R interval when vagal and sympathetic efferent pathways were intact. Reducing the stimulation voltage allowed selective stimulation of the myelinated (A) fibers, and polarizing electrodes placed central to the stimulus site permitted A fiber blockade and selective stimulation of the unmyelinated (C) fibers. When afferent A fibers were selectively stimulated, 64% of the maximum response was obtained; selective C fiber activation elicited 63% of the maximum observed response. Selective stimulation of A or C fibers after either vagotomy or stellectomy indicated that A fiber afferents elicit heart rate responses via both vagal and sympathetic efferents, whereas C fiber afferent information is mediated predominantly via vagal efferents. This afferent-efferent specificity of the aortic baroreceptor pathways suggests baroreceptor mechanisms normally used to modulate heart rate. Small increments in blood pressure would activate low-threshold A fibers and result in reciprocal changes in vagal and sympathetic efferent activity. More substantial increases in blood pressure would activate afferent C fibers and produce additional heart rate effects via vagal efferents.

Baroreceptor mechanisms controlling sympathetic nervous rhythms of central origin.

A study was made in the anesthetized cat of the slow wave of sympathetic nervous discharge (SND) locked in a 1:1 relation to the cardiac cycle (3 cycle/s periodicity). SND was recorded from the preganglionic splanchnic and postganglionic renal nerves. The data contradict the generally accepted view that the slow wave occurs as the direct result of a waxing and waning of baroreceptor nervous discharge. Although baroreceptor denervation unlocked the phase relations between SND and the cardiac cycle, the slow wave persisted and its duration was not changed. Furthermore, the slow wave was aborted by stimuli delivered to the baroreceptor nerves or paramedian reticular nucleus during a time span which accounted for less than 1 percent of the cardiac cycle. It is concluded that the 3 cycle/s periodicity of SND is representative of a vasomotor rhythm of central origin which is entrained to the cardiac cycle by the baroreceptor reflexes. The sympathoinhibitory effect leading to the entrainment of the slow wave is mediated in the brainstem. ta spinal component of baroreceptor-induced sympathoinhibition also was demonstrated.

The Role of Baroreceptors in the Cardiovascular Response to Ketamine

To elucidate the role of the intravascular baroreceptors in the cardiovascular stimulation associated with ketamine anesthesia, an experiment was devised in which the proposed inhibitory baroreceptor mechanism could be effectively blacked by carotid sinus nerve stimulation. In neurologically intact dogs which responded normally to ketamine before and after carotid sinus nerve stimulation, the cardiovascular effect of the drug was not altered by baroreceptor nerve stimulation. In light of this finding and those of other workers, the cardiovascular response to ketamine anesthesia most likely originates at some site in the central nervous system or at a peripheral sensor other than the baroreceptors.

Catecholamines and the secretion of renin, acth and growth hormone

Publisher Summary This chapter reviews the catecholamines and the secretion of renin, ACTH, and growth hormone. The effects of sympathetic stimulation on renin secretion could be mediated through the baroreceptor or macula densa mechanisms, because injected catecholamines and renal nerve stimulation can lower the pressure in the renal arterioles and reduce sodium delivery to the distal tubule, with a resultant decrease in sodium transport across the macula densa. α-Adrenergic blocking drugs do not inhibit the rise in renin produced by sympathetic stimulation, and most if not all of the hemodynamic effects of catecholamines on the kidney are mediated through αadrenergic receptors. Indeed, in a number of situations, a-adrenergic blockade potentiates renin secretion. The secretion of the anterior pituitary gland is also affected by catecholamines. Anterior pituitary secretion is regulated by a family of approximately eight releasing and inhibiting factors secreted by cells in the hypothalamus and the secretion of these releasing and inhibiting factors is in turn regulated to a large degree by norepinephrine and dopamine-secreting neurons in the diencephalon.

Role of trigeminal, olfactory, carotid sinus and aortic nerves in the respiratory and circulatory response to nasal inhalation of cigarette smoke and other irritants in the rabbit.

SummaryThe contributions of different afferent pathways to the reflex apnoea in expiration, mild hypertension and marked bradycardia evoked in unanaesthetized rabbits by nasal inhalation of cigarette smoke, formaldehyde, ammonia and benzene vapour were defined according to a factorial experimental design. Animals were used with (1) trigeminal nerve ablation, (2) olfactory bulb ablation, (3) total and selective section of the carotid sinus and aortic nerves, and (4) combinations of the above lesions. Trigeminal afferents are the primary source of the respiratory and circulatory disturbance. Olfactory afferents cannot initiate the respiratory and circulatory disturbance but weakly potentiate the apnoea induced by trigeminal stimulation. Arterial baroreceptor mechanisms contribute to the evoked bradycardia. Arterial chemoreceptor mechanisms do not contribute to the circulatory effects, but act to terminate the induced apnoea.

Catecholamines and the secretion of renin, acth and growth hormone

Publisher Summary This chapter reviews the catecholamines and the secretion of renin, ACTH, and growth hormone. The effects of sympathetic stimulation on renin secretion could be mediated through the baroreceptor or macula densa mechanisms, because injected catecholamines and renal nerve stimulation can lower the pressure in the renal arterioles and reduce sodium delivery to the distal tubule, with a resultant decrease in sodium transport across the macula densa. α-Adrenergic blocking drugs do not inhibit the rise in renin produced by sympathetic stimulation, and most if not all of the hemodynamic effects of catecholamines on the kidney are mediated through αadrenergic receptors. Indeed, in a number of situations, a-adrenergic blockade potentiates renin secretion. The secretion of the anterior pituitary gland is also affected by catecholamines. Anterior pituitary secretion is regulated by a family of approximately eight releasing and inhibiting factors secreted by cells in the hypothalamus and the secretion of these releasing and inhibiting factors is in turn regulated to a large degree by norepinephrine and dopamine-secreting neurons in the diencephalon.

Baro- and chemoreceptor mechanisms in haemorrhage.

The observations summarized here arose out of a systematic examination, made for other purposes, of the effects of haemorrhage in animals of different ages, lightly anaesthetized with sodium barbitone. It became evident that in terms of the criteria detailed below, kittens and young rabbits withstood haemorrhage better than the adults of these species (10, 14). Further analysis showed that the contribution of arterial baroreceptor mechanisms in the maintenance of arterial pressure is relatively greater in adult rabbits and that mechanisms of renal origin have a predominant influence in immature rabbits (15). Both these species, especially the rabbit, are born in a somewhat immature condition. Developmental changes in cardiovascular function must be taken into account when designing appropriate tests of, and in assessing cardiovascular responses to, stimuli.

Baroreceptor Function in Hypertensive and Normotensive Patients with Uremia.

Meeting Abstracts1 May 1972Baroreceptor Function in Hypertensive and Normotensive Patients with Uremia.J. M. Lazarus, M.D., C. L. Hampers, M.D., J. P. Merrill, M.D.J. M. Lazarus, M.D.Search for more papers by this author, C. L. Hampers, M.D.Search for more papers by this author, J. P. Merrill, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-76-5-875_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptA group of patients were on hemodialysis with persistent hypertension despite maximum ultrafiltration and bilateral nephrectomy. In a pilot study of 140 hemodialysis patients, an increased frequency and severity of posturalhypotension was found inhypertensive uremic patients and suggests an abnormality in the baroreceptor mechanism. To further evaluate a "resetting" of the baroreceptor mechanism the effects of standing and drug-induced blood pressure changes were serially studied in four normotensive and nine hypertensive (> 150/90 mm Hg) patients before and after nephrectomy. Baroreceptor function was evaluated by the pulse response to elevation and lowering of blood pressure with angiotensin and... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byHemodynamic lesions in hypertension 1 May 1972Volume 76, Issue 5Page: 875-875KeywordsBlood pressureDrugsHeart rateHypertensionHypotensionNephrectomyPilot studiesUltrafiltration ePublished: 1 December 2008 Issue Published: 1 May 1972 PDF downloadLoading ...

Effects of renal venous pressure elevation on renal hemodynamics, urine formation and renin release.

Effects of renal venous pressure (RVP) elevation on the renal hemodynamics, urine formation and renin secretion rate (RSR) were studied in the pentobar-bital anesthetized dogs. Gradual increment of RVP produced no changes in RBF and GFR till 30 mmHg but a significant decrease in them at RVP above 35 mmHg. The urine flow response to RVP elevation was divided into two groups: an increased urine flow with an increase of sodium excretion and a decreased urine flow with a decrease of sodium excretion. In the former group, gradual RVP elevation produced a significant increase in UNaV, Na/K ratio and TCH20 without changes in UKV and Cosm, while the latter group showed a decrease in UNaV, UKV and TCH20. Renin secretion rate (RSR), the product of RPF and renal venous-arterial difference of plasma renin activity, increased significantly as function of RVP elevation. This RSR increment seemed to be independent of changes in RBF, GFR, urine flow, or UNaV and the increased mechanism of RSR was discussed. It is concluded that tubular handling of sodium is not essential but intrarenal baroreceptor mechanism seems to be responsible for renin release in case of RVP elevation.