Biomedical subjects

C N May

Publications and source records attributed to C N May.

At least 37 records · Page 2Linked to original sources

PubMed1997

Investigation of the mineralocorticoid and hypertensinogenic activity of 18-hydroxycortisol in conscious sheep.

The increased urinary excretion of 18-hydroxycortisol (18-OHF) in patients with primary aldosteronism has raised the possibility that 18-OHF is involved in the maintenance and/or pathogenesis of the associated hypertension. This study has investigated the mineralocorticoid, glucocorticoid, and hypertensinogenic activities of 18-OHF in the conscious sheep. Infusion of 18-OHF (400 micrograms/h i.v. 5 days; n = 5) alone had no effect on blood pressure or on fluid and electrolyte balance. Infusion of a combination of five adrenal steroids (aldosterone 3 micrograms/h, cortisol 5 mg/h, corticosterone 0.5 mg/h, 11-deoxycortisol 1 mg/h and deoxycorticosterone 25 micrograms/h, i.v. 5 days; n = 5) increased blood pressure by 14 +/- 1 mmHg (p < .001), but when 18-OHF was infused together with the five adrenal steroids, no additional increase in blood pressure was observed. In another group of sheep (n = 4) 18-OHF was infused at a range of doses (5, 50, 100, 200, 500, and 1000 micrograms/h i.v.), each for 2 h, into sodium-replete and sodium-deplete, adrenalectomized sheep. 18-OHF had no effect on the urinary sodium or potassium excretion or on the salivary Na/K ratio in either group as compared with vehicle infusion. To examine the renal effects of 18-OHF, a range of doses of 18-OHF (5, 50, 100, 200, 500, and 1000 micrograms/h) were infused directly into the renal artery of conscious sheep (n = 4). 18-OHF did not affect the renal blood flow nor the urinary sodium or potassium excretion compared with vehicle infusion. In summary, we could not demonstrate any mineralocorticoid, glucocorticoid, or hypertensiongenic effects of 18-OHF in conscious sheep at a dose of 400 micrograms/h. Thus, a cautious approach to interpreting the role that 18-OHF plays in the clinical manifestations of primary aldosteronism, is necessary.

Adrenalectomy↗

PubMed1997

Direct cardiac and vascular actions of adrenomedullin in conscious sheep.

1. Adrenomedullin (ADM) is a recently characterized circulating hormone which affects haemodynamic, renal and pituitary function in mammals. We have shown previously that in sheep, ADM produces vasodilatation together with increases in cardiac output and contractility. However, whether these effects are direct or mediated by autonomic reflexes is unclear. The present study examined the cardiovascular actions of an intravenous infusion of ADM in conscious, chronically instrumented sheep with either sympathetic, parasympathetic or autonomic ganglion blockade, to determine the role of the autonomic nervous system in mediating these cardiovascular changes. 2. Human ADM (1-52) was infused for 60 min at 2 micrograms kg-1 h-1 following: (1) saline control, (2) combined alpha/beta-adrenoceptor (sympathetic) blockade (proporanolol 0.4 mg kg-1 h-1 + phentolamine 0.15 mg kg-1 h-1 for 20 h), (3) muscarinic (parasympathetic) blockade (methscopolamine 0.05 mg kg-1 h-1 for 20 h) or (4) ganglion blockade (hexamethonium 3 mg kg-1 h-1 for 4 h). Measurements were made of mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC), maximal aortic flow (Fmax) and maximal rate of change of aortic flow (dF/dt). 3. ADM reduced MAP by 3 +/- 1 mmHg, and increased CO (1.2 +/- 0.2 l min-1), HR (14 +/- 2 beats min-1), TPC (21 +/- 3 ml min-1 mmHg-1). Fmax (2.3 +/- 0.8 l min-1) and dF/dt (86 +/- 21 l min-1 s-1) in normal sheep. In animals with alpha/beta blockade, similar changes were observed with ADM. However, during muscarinic blockade, the increases in HR (32 +/- 4 beats min-1), CO (2.1 +/- 0.4 l min-1), TPC (31 +/- 4 ml min-1 mmHg-1). Fmax (4.0 +/- 0.6 l min-1), and dF/dt (150 +/- 12 l min-1 s-1) produced by ADM were enhanced. During ganglion blockade, ADM produced a greater reduction in MAP (-10 +/- 2 mmHg) compared to controls (-3 +/- 1 mmHg). However, there was no increase in HR. The changes in CO, TPC and contractility were similar to those observed in control animals. 4. These results suggest that the vasodilator effects of ADM on the periphery and its ability to increase CO and cardiac contractility are not mediated by the autonomic nervous system, but are probably the result of direct actions of ADM on the heart and vasculature.

Adrenergic Antagonists↗

PubMed1997

Cardiac inotropic actions of urocortin in conscious sheep.

Urocortin (Ucn) is a recently isolated peptide related to the corticotropin-releasing factor (CRF) family, which can produce hemodynamic and hormonal actions in conscious rats. This study examined in detail the cardiovascular actions of Ucn and CRF after intravenous injection in chronically instrumented, conscious sheep. Injection of Ucn produced dose-dependent changes in cardiac contractility [rate of increase of aortic flow (dF/dt)], maximum aortic flow (Fmax), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and coronary blood flow (CF). Ucn injected at 100 micrograms produced a potent increase in dF/dt, from 909 +/- 44 to a maximum of 1,849 +/- 901.min-1.s-1, and in Fmax, from 25.5 +/- 0.8 to 36.6 +/- 1.4 l/min. Cardiac contractility increased within 30 min of injection and remained significantly elevated for up to 24 h. MAP increased from 78 +/- 2 to 90 +/- 3 mmHg, and HR increased from 73 +/- 4 to 103 +/- 9 beats/min. CO rose from 5.0 +/- 0.1 to 5.8 +/- 0.2 l/min, whereas central venous pressure, total peripheral conductance, and stroke volume were unchanged. All Ucn-induced cardiovascular effects were inhibited by prior treatment with the CRF antagonist alpha-helical CRF-(9-41). Equimolar doses of CRF produced little change in any hemodynamic parameter. Both peptides increased plasma levels of adrenocorticotropin and cortisol, with Ucn having a more potent effect than CRF. We have shown for the first time that Ucn can produce potent and long-lasting actions to elevate cardiac contractility in conscious animals.

Adrenocorticotropic Hormone↗

PubMed1997

Separation of peripheral and central cardiovascular actions of angiotensin II.

The pressor and vasoconstrictor action of angiotensin II (ANG II) is considered to be caused by a combination of its direct and indirect vascular effects, the latter mediated by the sympathetic nervous system. The purpose of this study was to determine the extent to which the direct and indirect actions of ANG II contribute to its pressor and vascular effects. Blood pressure, cutaneous vascular, and plasma norepinephrine responses to intravenous ANG II were measured in conscious rabbits before and after inhibition of central sympathetic outflow with intravenous and intracisternal clonidine and after ganglionic blockade with intravenous pentolinium. Intravenous ANG II caused a similar dose-related rise in blood pressure before and after sympathetic blockade with intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. In contrast, the dose-related fall in cutaneous ear blood flow and cutaneous ear temperature and rise in cutaneous ear vascular resistance induced by intravenous ANG II were abolished after intravenous clonidine, intracisternal clonidine, and intravenous pentolinium. Heart rate was unchanged after ANG II. There were no changes in back skin or rectal temperature. There was a nonsignificant fall in plasma norepinephrine and no change in epinephrine after ANG II. These results demonstrate that the acute pressor response to intravenous ANG II is mediated by its direct vascular effects and is not dependent on central or ganglionic stimulation of the sympathetic nervous system, in contrast to the effect of ANG II on cutaneous ear vasoconstriction, which is predominantly caused by a centrally mediated increase in sympathetic nervous activity. Our results separate, in conscious rabbits, the direct vascular effects of ANG II from its indirect vascular actions, which are mediated by central sympathetic stimulation in the brain.

Angiotensin II↗

PubMed1997

Brain angiotensinergic pathways mediate renal nerve inhibition by central hypertonic NaCl in conscious sheep.

The renal sympathetic responses to infusion of hypertonic solutions into the lateral cerebral ventricles were investigated in conscious sheep. Intracerebroventricular infusion of artificial cerebrospinal fluid (CSF) containing 0.6 M NaCl, at 1 ml/h for 20 min, reduced renal sympathetic nerve activity (RSNA) by 81 +/- 5% (n = 6, P < 0.001). Plasma renin concentration also fell (P < 0.05), whereas arterial pressure increased by 6.4 +/- 0.7 mmHg (P < 0.01). Intracerebroventricular hypertonic sorbitol (0.9 M in CSF at 1 ml/h) had no effect. The AT1 receptor antagonist losartan (1 mg/h) abolished the plasma renin and arterial pressure responses to intracerebroventricular hypertonic saline and significantly reduced the fall in RSNA to 17 +/- 10% (P < 0.001). During intracerebroventricular hypertonic saline, the baroreflex relation of RSNA to diastolic pressure was shifted to the left and that to central venous pressure was abolished compared with control relations obtained by manipulating pressure with intravenous phenylephrine. These findings indicate that 1) RSNA is inhibited by a central mechanism that senses high sodium (or perhaps chloride) concentration rather than hypertonicity; 2) this inhibition occurs independently of reflexes from high- and low-pressure baroreceptors, although these may enhance the inhibition; and 3) inhibition of RSNA by hypertonic saline involves a central angiotensinergic pathway.

Angiotensin II↗

PubMed1997

Baroreceptor-independent renal nerve inhibition by intracerebroventricular angiotensin II in conscious sheep.

The effect of central administration of angiotensin II (ANG II) on efferent renal sympathetic nerve activity (RSNA) was studied in conscious sheep. ANG II (1 nmol/h), infused for 30 min into the lateral cerebral ventricles in five sheep, did not alter mean arterial pressure (MAP) but reduced RSNA to 38 +/- 5% of control. Intracerebroventricular infusion of higher doses of ANG II (3 and 10 nmol/h), which increased MAP by 12 +/- 2 and 14 +/- 3 mmHg, respectively, reduced RSNA to 9 +/- 5 and 11 +/- 7% of control. MAP and RSNA gradually returned to control over a period of 2 h after the infusions. Intracerebroventricular losartan (1 mg/h for 1 h before, and then during, angiotensin infusion) blocked all the effects of angiotensin (3 nmol/h). Baroreflex relationships constructed from the beat-to-beat relationship of RSNA to diastolic pressure showed a significant leftward shift during intracerebroventricular ANG II compared with the control relationship. The beat-to-beat relationship between central venous pressure and RSNA was abolished during intracerebroventricular infusion of ANG II. These findings demonstrate that intracerebroventricular ANG II has a direct central inhibitory action on RSNA that is independent of both arterial and low-pressure baroreceptors. This effect of angiotensin is mediated by central angiotensin AT-1 receptors.

Angiotensin II↗

PubMed1997

Glucocorticoid-induced renal vasodilatation is mediated by a direct renal action involving nitric oxide.

Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate, but the mechanisms are unclear. We investigated whether the cortisol-induced increment in RBF is a direct renal action or secondary to its systemic effects and whether nitric oxide (NO) plays a role in this response. In conscious sheep, cortisol infused intravenously (5.0 mg/h) or into the renal artery (1.3 mg/h) for 5 h increased RBF by 66 +/- 8 and 53 +/- 11 ml/min, respectively. Plasma glucose was increased by intravenous cortisol (0.4 +/- 0.1 mmol/l) but not by intrarenal cortisol. Renal vein plasma cortisol levels were similar at the end of each infusion (193 +/- 31 intravenously; 151 +/- 25 nmol/l intrarenal), but systemic levels were different (277 +/- 31 intravenous; 69 +/- 10 nmol/l intrarenal). Inhibition of NO synthesis by N omega-nitro-L-arginine infused intravenously (10 mg/kg followed by 5 mg.kg-1.h-1) or intrarenally (2 mg.kg-1.h-1) significantly reduced the cortisol-induced renal vasodilatation. In contrast, constriction of the renal vasculature with intrarenal angiotensin (0.3 microgram/h) did not prevent the cortisol-induced renal vasodilatation. These findings demonstrate that cortisol acts directly on the kidney to cause renal vasodilatation and to increase RBF and suggest that this response involves the endothelium-derived relaxing factor NO.

Animals↗

PubMed1996

Role of nitric oxide in the attenuated pressor responses of pregnant or sodium-deplete sheep.

Reduced pressor responsiveness to angiotensin II (Ang II) during pregnancy and sodium depletion is a well-known but little understood phenomenon; whether the same mechanisms are involved in both situations is unclear. In pregnant humans, altered vascular reactivity to norepinephrine (NE) has also been demonstrated. Nitric oxide (NO) has been implicated in the modulation of blood pressure (BP) and the maintenance of vascular tone and may be involved in these attenuated responses. We examined the role of NO in the pressor responses to (a) Ang II (5, 10, 25, 50 micrograms/h) and NE (0.32, 0.65, 1.62, 3.24 mg/h) in pregnant and postpartum sheep, and (b) to Ang II (5, 7, 5, 10, 25, 50 micrograms/h) in sodium-replete sheep and sheep made sodium deplete by 24 h of parotid salivary drainage. Vascular NO production was inhibited by pretreatment with N omega-nitro-L-arginine (NOLA 10 mg/kg), a NO-synthase inhibitor. Pregnancy significantly reduced (p < 0.001) pressor responses to Ang II, which ranged from 5.1 +/- 0.2-30.6 +/- 1.2 mm Hg as compared with postpartum increases of 10.3 +/- 0.5-52.2 +/- 3.4 mm Hg. Pretreatment with NOLA partially restored Ang II responses to postpartum levels. Pregnancy did not alter pressor responses to NE. Sodium depletion also significantly reduced responses to Ang II by the same amount as in pregnancy, and these responses returned to normal with pretreatment with NOLA. NO thus has a role in modulating the attenuated pressor responses to Ang II in pregnant and sodium-deplete sheep.

Angiotensin II↗

PubMed1996

Evidence against a central pressor mechanism for adrenocortical steroid hypertension in sheep.

The possibility that corticotropin (ACTH)-induced hypertension results from a direct central effect of the adrenocortical steroids released by ACTH was investigated in sheep. Using two approaches, steroid levels were increased in the brain while peripheral levels remained sub-pressor. The blood pressure response to intravenous infusion of a combination of 7 steroids (aldosterone, cortisol, deoxycorticosterone, corticosterone, 11-deoxycortisol, 17 alpha hydroxyprogesterone and 17 alpha 20 alpha dihydroxyprogesterone), which causes a similar pressor effect to ACTH, was compared with that caused by intracarotid infusion of the steroids at rates calculated to give concentrations in the brain equivalent to those achieved after intravenous infusion. We also examined the effects of infusing the combination of steroids directly into the central nervous system via the lateral cerebral ventricles. Intravenous infusion of the steroids increased mean arterial pressure (MAP) from a control average of 84.0 +/- 1.1mmHg to 98.2 +/- 2.2mmHg (p < 0.001) on day 5. There was no increase in MAP during intracarotid infusion, nor during intracerebroventricular infusion. These findings suggest that the adrenocortical steroids released by ACTH do not act directly on central steroid receptors to increase blood pressure.

Adrenocorticotropic Hormone↗

PubMed1996

Brainstem neurones and postganglionic sympathetic nerves: does correlation mean connection?

Short-term correlations in activity have been widely used as evidence to connect brainstem units with postganglionic sympathetic nerves. These may be detected by spike-triggered averaging, cross correlation or coherence analysis. The specificity of this type of evidence has been investigated by cross-correlating the activity of identified cutaneous vasoconstrictor postganglionic fibres with that of medullary premotor neurones of like and of unlike functional type, as determined by physiological testing (preoptic warming), in anaesthetised cats. Single medullary premotor neurones of both types were recorded from the subretrofacial nucleus: they were identified by their barosensitivity and, in most cases, their spinally projecting axons. By the test criteria chosen, the correlation method gave both false-positive and false-negative results as commonly as it gave correct ones. We conclude that it is not a reliable way to determine brainstem-postganglionic connectivity.

Animals↗

PubMed1996

Effects of infusion of combinations of adrenocorticosteroids on systemic and regional haemodynamics in conscious sheep.

OBJECTIVE: To compare the cardiovascular, metabolic and endocrine responses to infusions of two combinations of adrenocorticosteroids and to determine their contribution to the haemodynamic effects of corticotrophin. METHODS: The effect of 5 day's infusion of combinations of seven corticosteroids (aldosterone, cortisol, corticosterone, 11-deoxycorticosterone, 11-deoxycortisol, 17 alpha-hydroxyprogesterone and 17 alpha-hydroxy-20 alpha-dihydroprogesterone and five corticosteroids (17 alpha-hydroxyprogesterone and 17 alpha,20 alpha-hydroxyprogesterone omitted) on arterial pressure, cardiac output (measured using electromagnetic flow probes) and regional blood flows (measured using transit-time flow probes) was determined in conscious sheep. RESULTS: Combined infusion of seven steroids increased mean arterial pressure from 79 +/- 2 to 91 +/- 2 mmHg (day 5). Cardiac output increased from 5.42 +/- 0.22 to 6.55 +/- 0.41 l/min owing to an increase in stroke volume. Mesenteric conductance fell from 6.3 +/- 0.4 to 5.4 +/- 0.5 ml/min per mmHg, and renal conductance increased from 3.1 +/- 0.1 to 4.0 +/- 0.1 ml/min per mmHg, resulting in no change in total peripheral conductance. There were only minor effects on the coronary and iliac vascular beds. Infusion of five steroids caused similar changes in mean arterial pressure (from 78 +/- 1 to 89 +/- 2 mmHg on day 5), cardiac output and regional blood flows. The cardiovascular, fluid, electrolyte and endocrine responses to both steroid treatments were similar to those with corticotrophin. CONCLUSIONS: Infusion of combinations of seven or five adrenocortical steroids reproduced the cardiovascular actions of corticotrophin, namely increases in arterial pressure, and cardiac output, mesenteric vasoconstriction and renal vasodilation. This contrasts with previous studies in which only an infusion of steroids including 17 alpha-hydroxyprogesterone and 17 alpha,20 alpha-OHP reproduced the pressor effect of corticotrophin fully, possibly because in these sheep, as has been proposed to be the case in humans, the dose-response curves for the hypertensinogenic, mineralocorticoid and glucocorticoid actions overlap.

Adrenal Cortex Hormones↗

PubMed1995

Effect of ICV infusion of CRF on blood pressure and adrenal steroids in rabbits.

The effect of prolonged, 22 h long, intracerebroventricular (i.c.v.) infusion of corticotropin-releasing hormone (CRF) on plasma cortisol, corticosterone and electrolyte concentrations, mean arterial blood pressure (MAP) and heart rate (HR) were investigated in conscious rabbits. During i.c.v. infusion of CRF, 1 and 3 micrograms/h, at a rate of 17 microliters/h, plasma cortisol and corticosterone concentrations rose to the level noted after ACTH stimulation in rabbits. Plasma [Na] did not change, but plasma [K] was reduced and plasma osmolality increased during the infusion of CRF, 3 micrograms/h. MAP and HR, recorded continuously during i.c.v. infusion of CRF, changed only with the higher dose of CRF: MAP was elevated during the first 5 h of infusion, and then returned to the control level. HR was lower than control at the end of the first hour of infusion and again between 9 and 15 h of infusion. The prolonged rise of CRF concentration in the brain induced a sustained rise in circulating adrenal steroid hormones. MAP did not increase to the level noted after bolus i.c.v. injection of CRF and the rise in MAP was not sustained.

Animals↗

PubMed1995

ACTH-suppressive and vasodilator actions of adrenomedullin in conscious sheep.

Adrenomedullin (ADM) is a 52 amino-acid peptide which is a potent vasodilator in rats, and suppresses basal and CRF-induced ACTH release from cultured pituitary cells. The present study examines the hemodynamic and hormonal actions of human ADM (1-52) infusion in conscious, chronically instrumented sheep. Five sheep were infused intravenously (IV) or intracerebroventricularly (ICV) with ADM at 100 micrograms/h for 60 min, and mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC), coronary blood flow (CF), coronary conductance (CC), peak aortic flow (Fmax), and left ventricular dF/dt were monitored by a computer-based data collection system every 2 min. Plasma concentrations of adrenocorticotropin (ACTH), arginine vasopressin (AVP) and renin were measured after 60 min of infusion. IV ADM produced a small fall in MAP of 3 +/- 1 mmHg, associated with a reflex increase in HR of 14 +/- 3 b/min. CO increased by 1.3 +/- 0.3 l/min, whereas SV remained unchanged. TPC was markedly increased by 20 +/- 3 ml/min/mmHg. Changes in CF were also seen with an increase of 10 +/- 2 ml/min, and CC increased in parallel by 0.15 +/- 0.02 ml/min/mmHg. Fmax and dF/dt showed small increases of 2.1 +/- 0.5 l/min and 85 +/- 20 l/min/sec respectively. Plasma concentrations of ACTH and cortisol were reduced by 58% and 55% respectively, whereas plasma renin concentration increased by 106%. There was no change in plasma levels of AVP. ICV infusion of ADM had no effect on any parameter measured. These data suggest that systemic ADM produces a sustained vasodilator action to lower blood pressure in sheep, and this is the first study to report the ACTH-suppressor action of ADM in conscious animals. ADM may therefore be an important hormone involved in the regulation of pituitary/adrenal function, in addition to its cardiovascular and fluid regulatory actions in mammals.

Adrenocorticotropic Hormone↗

PubMed1995

Evaluation of a transit-time system for the chronic measurement of blood flow in conscious sheep.

The accuracy of transit-time ultrasonic flow probes for measurement of regional blood flow and cardiac output was evaluated after long-term implantation in sheep. Transit-time flow probes (3, 4, 6, and 20 mm) accurately measured flow in vitro. Recalibration in vivo demonstrated that this accuracy was maintained after 1-9 mo of implantation on the left circumflex coronary (3-mm probe), cranial mesenteric (6-mm probe), left renal (4-mm probe), and left external iliac (6-mm probe) arteries of sheep. The flow probes also showed good zero stability. However, a transit-time flow probe (20 mm) chronically implanted on the pulmonary trunk significantly underestimated cardiac output compared with thermodilution or timed collection of blood. Although this flow probe underestimated flow, the response was linear. Bilateral carotid occlusion caused mesenteric, renal, and iliac vasoconstrictions, confirming that innervation of these vascular beds was undamaged. For experimental purposes, regional blood flow was measured with transit-time flow probes and cardiac output was measured with electromagnetic flow probes calibrated against thermodilution. In summary, transit-time flow probes reliably and accurately measure regional blood flow over many months in adult sheep, but, to measure cardiac output in sheep, the probes must be calibrated in vivo against another reference technique.

Animals↗

PubMed1995

Regional hemodynamic and endocrine effects of aldosterone and cortisol in conscious sheep. Comparison with the effects of corticotropin.

We studied the cardiovascular responses to 5 days' infusion of aldosterone (10 micrograms/h) and cortisol (5 mg/h) to determine the possible contribution of mineralocorticoid and glucocorticoid actions to the regional hemodynamic changes caused by corticotropin. These infusion rates produce plasma levels similar to those seen during corticotropin stimulation. In five conscious sheep aldosterone progressively increased mean arterial pressure (P < .001) to a maximum of 11 mm Hg on day 5, whereas cortisol increased pressure by 5 mm Hg (P < .01) within 24 hours. Cardiac outputs on the control day and on day 5 of infusion were 4.4 +/- 0.3 and 4.9 +/- 0.3 L/min, respectively, for aldosterone and 4.3 +/- 0.4 and 5.0 +/- 0.4 L/min for cortisol. Neither steroid significantly altered total peripheral conductance, but they had different, nonuniform regional hemodynamic effects. Mesenteric conductance fell progressively with aldosterone from 7.14 +/- 0.35 (mL/min)/mm Hg to a minimum of 6.17 +/- 0.38 (P < .01) on day 5 of infusion. Mesenteric conductance was transiently reduced with cortisol, but this was not significant over the 5 days. Renal conductance was unchanged with aldosterone, but cortisol caused a rapid, sustained increase in renal conductance from 2.9 +/- 0.3 to 4.0 +/- 0.4 (mL/min) / mm Hg (P < .001) within 24 hours, similar to the increase caused by corticotropin. As with corticotropin there were only minor changes in the coronary and iliac vascular beds. In summary, these two endogenous steroids had contrasting, nonuniform regional hemodynamic effects, aldosterone causing mesenteric vasoconstriction, and cortisol causing renal vasodilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1994

Effects of preoptic warming on subretrofacial and cutaneous vasoconstrictor neurons in anaesthetized cats.

1. Sympathetic and subretrofacial neuron responses to preoptic warming were studied in chloralose- or Saffan-anaesthetized, paralysed cats. 2. Warming a thermode in the preoptic region inhibited the activity of cutaneous vasoconstrictor fibres supplying hairy skin. Muscle vasoconstrictor fibre activity recorded at the same time was either unaffected or raised. 3. Small injections of sodium glutamate (5 nl, 0.1 M) were made into the region of the subretrofacial nucleus in the ventrolateral medulla. The part of that region where glutamate injections evoked brisk increases in cutaneous vasoconstrictor fibre activity was chosen for further study. 4. Extracellular single unit recordings were made in that area from seventy-seven subretrofacial neurons, which were identified by their barosensitivity (inhibition by carotid blind sac inflation). Forty-seven of them were antidromically activated by stimulation in the spinal cord. 5. The activity of twenty subretrofacial neurons (twelve proven bulbospinal) was significantly reduced by periods of preoptic warming. Cutaneous vasoconstrictor activity recorded at the same time also fell. Forty-nine subretrofacial neurons (thirty-five proven bulbospinal) were unaffected or excited by periods of preoptic warming that inhibited cutaneous vasoconstrictor fibres. The response of eight neurons was unclear. 6. No difference in either mean firing rate or axonal conduction velocity was found between neurons inhibited by preoptic warming and other subretrofacial neurons. 7. The subretrofacial neurons inhibited by warming were found intermingled with those unaffected or excited. Marked recording sites of warm-inhibited neurons were clustered around the ventromedial border of the subretrofacial nucleus. 8. In two cats, bilateral inhibition of subretrofacial neurons by surface application of 1 M glycine reduced cutaneous vasoconstrictor fibre activity to 32 and 44% of control levels. 9. The results suggest that specific cutaneous vasoconstrictor premotor neurons exist in the subretrofacial nucleus. These apparently provide most of the background excitatory drive to cutaneous vasomotor neurons. Central warming stimuli may act, at least in part, by withdrawing that drive.

Anesthesia↗

PubMed1994

Prolonged regional vasoconstriction produced by NG-nitro-L-arginine in conscious sheep.

Nitric oxide (NO) is a potent endothelium-derived vasodilator whose synthesis can be blocked both in vitro and in vivo by structural analogues of its precursor, L-arginine (L-ARG). We examined the dose-response profile of one such analogue, NG-nitro-L-arginine (NOLA) in conscious sheep (n = 4) and used continuous monitoring techniques to study long-term changes in mean arterial pressure (MAP), heart rate (HR), and cardiac output (CO) and the relative responsiveness of the coronary, mesenteric, renal, and hindlimb vascular beds to NOLA [10 mg/kg, intravenous (i.v.) bolus] in 5 sheep. NOLA (3 and 10 mg/kg) increased MAP at 1 h from 73 +/- 4 to 86 +/- 3 mm Hg (p < 0.05) and 73 +/- 1 to 106 +/- 8 mm Hg (p < 0.05), respectively. CO and HR decreased significantly after 10 mg/kg NOLA. Plasma endothelin (ET) level was unchanged after all doses of NOLA. Continuous monitoring of MAP, CO, and blood flow for 24 h before and after NOLA injection showed that MAP increased rapidly owing to a decrease in total peripheral conductance (TPC), with short-term reflex decreases in HR and prolonged decreases in CO and stroke volume (SV). Coronary and iliac conductances changed comparatively little. Renal conductance decreased by 43% at 80 min, but was not different from control after 6 h. The greatest and most sustained decrease in conductance, by a maximum of 55% of control levels at 110 min, occurred in the mesenteric bed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Differential drives from rostral ventrolateral medullary neurons to three identified sympathetic outflows.

Simultaneous recordings were made in chloralose-anesthetized cats from muscle vasoconstrictor (MVC), visceral vasoconstrictor (VVC), and renal (RSN) sympathetic fibers. Their barosensitivity was demonstrated, after which all baroreceptor nerves were cut. Multiple microinjections of sodium glutamate (5 nl, 0.1 M) were made in a grid pattern covering the rostral ventrolateral medulla (RVLM) pressor area on seven sides of four animals. Injections increased blood pressure by up to 87 +/- 22 mmHg and MVC, VVC, and RSN activities by up to 169 +/- 55, 62 +/- 23, and 67 +/- 36%, respectively. The relative responses between nerves (taken in pairs) showed significant inhomogeneity across injections into 5/7, 6/7, and 1/7 RVLMs for MVC vs. VVC, MVC vs. RSN, and VVC vs. RSN, respectively. Calculation showed that overall, less than half the response spikes due to RVLM glutamate injections could be accounted for by a hypothetical population of neurons that excited MVC, VVC, and RSN outflows in fixed proportion. Sites that exclusively drove MVC, VVC, or RSN outflows were found in 7/7, 3/7, and 5/7 RVLMs, respectively. Sites that selectively drove either nerve of a given pair were ubiquitous. The RVLM territories from which the three outflows could be activated overlapped but showed clear differences. Their shapes and sizes differed between animals and even between sides. They covered the subretrofacial (SRF) nucleus plus a variable rostromedial extension. The data support the view that the RVLM neurons driving these three sympathetic outflows are largely, perhaps entirely, separate populations.

Animals↗