Effects of opioid antagonism on the haemodynamic and hormonal responses to exercise

1. Physical effort involves, along with an increase in the plasma concentration of β-endorphin, profound adaptations of the circulation and the endocrine system. The effects of opioid antagonism on the responses of blood pressure, heart rate and several hormones to exercise were therefore studied in 10 normal men. They exercised in the supine position up to 33% and 66% of their maximal exercise capacity and received in a randomized double-blind cross-over protocol, either saline or naloxone (10 mg intravenously, followed by a continuous infusion of 10 mg/h). 2. Intra-arterial pressure and heart rate were continuously monitored, but were not affected by naloxone. 3. At rest, opioid antagonism produced a rise in plasma renin activity and in plasma adrenocorticotropin, Cortisol and aldosterone, but only the stimulation of the two adrenocortical hormones differed significantly from the control experiments; at rest naloxone also prevented the fall in plasma adrenaline, which occurred with saline infusion. Furthermore, the exercise-induced rises in plasma angiotensin II, aldosterone, Cortisol, noradrenaline and adrenaline were higher on naloxone than on saline, while a similar tendency was also present for the increases with exercise in plasma renin activity and plasma adrenocorticotropin. Neither at rest nor during exercise did opioid antagonism alter plasma lactate and glucose and serum insulin and growth hormone. 4. In conclusion, (1) endogenous opioids are not involved in the responses of blood pressure and heart rate to supine exercise; (2) at rest and during exercise, the endogenous opioids inhibit the secretion of adrenocorticotropin, aldosterone, Cortisol, noradrenaline and adrenaline; (3) they also inhibit the plasma renin-angiotensin II system indirectly via the catecholamines.

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Plasma Catecholamines and Plasma Renin Activity at Birth and during the First Days of Life

Clinical Science ◽

10.1042/cs059319s ◽

1980 ◽

Vol 59 (s6) ◽

pp. 319s-321s ◽

Cited By ~ 5

Author(s):

G. Leonetti ◽

C. Bianchini ◽

G. B. Picotti ◽

A. Cesura ◽

Letizia Caccamo ◽

...

Keyword(s):

Blood Pressure ◽

Plasma Renin Activity ◽

Umbilical Cord Blood ◽

Plasma Catecholamines ◽

Plasma Renin ◽

Renin Activity ◽

Plasma Noradrenaline ◽

Plasma Adrenaline ◽

Noradrenaline And Adrenaline ◽

Noradrenaline Levels

1. Plasma noradrenaline and adrenaline concentrations and plasma renin activity were measured in 21 mothers at delivery and in their babies at birth (umbilical cord blood) and on days 1 and 5 of extrauterine life. 2. At birth plasma renin activity was significantly higher in the newborn than in mothers. Plasma renin activity increased further, but not significantly, on day 1 of life and significantly decreased on day 5. On day 5, 10 min head-up tilting caused no change in plasma renin activity. 3. Plasma noradrenaline in the newborn was higher than in mothers at birth and significantly decreased thereafter. Plasma adrenaline levels at birth were similar in the newborn and their mothers and significantly lower in the newborn in subsequent days. Tilting caused no increase in either plasma adrenaline or noradrenaline levels. 4. No correlation was found between plasma noradrenaline and adrenaline levels and plasma renin activity, or between noradrenaline, adrenaline or plasma renin activity and blood pressure.

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Effect of an opiate antagonist on the responses of circulating catecholamines and the renin-aldosterone system to acute sympathetic stimulation by hand-grip in man

Acta Endocrinologica ◽

10.1530/acta.0.1110252 ◽

1986 ◽

Vol 111 (2) ◽

pp. 252-257 ◽

Cited By ~ 16

Author(s):

K. S. L. Lam ◽

A. Grossman ◽

P. Bouloux ◽

P. L. Drury ◽

G. M. Besser

Keyword(s):

Blood Pressure ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Endogenous Opioids ◽

Renin Activity ◽

Mild Stress ◽

Sympathetic Stimulation ◽

Plasma Adrenaline ◽

Hand Grip ◽

Serum Aldosterone

Abstract. The effect of naloxone on the neurohumoral responses to acute sympathetic stimulation by sustained hand-grip in normal man was investigated. Six normal males were studied fasting at 08.30 h, on two occasions at 7-day intervals, with each subject sustaining 30% of his maximal hand-grip on a hand dynamometer for 5 min. Naloxone (8 mg bolus) in 20 ml normal saline, or saline alone, was given 5 min before hand-grip in a randomised double-blind cross-over trial. Blood was sampled for plasma renin activity, serum aldosterone and plasma catecholamines. The study was repeated in the absence of hand-grip. Sustained hand-grip produced significant elevations in mean blood-pressure, circulating adrenaline, noradrenaline and aldosterone. Naloxone, which had no effect on basal catecholamines, plasma renin activity or aldosterone, significantly enhanced the responses in plasma adrenaline, plasma renin activity and serum aldosterone to hand-grip. The increments in blood pressure and noradrenaline were not affected. These results suggest that endogenous opioids modulate the response of the sympathoadrenal and renin-aldosterone systems to acute sympathetic stimulation by a mild stress in man.

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Plasma renin activity, angiotensin II, and aldosterone during intense heat stress

Journal of Applied Physiology ◽

10.1152/jappl.1976.41.3.323 ◽

1976 ◽

Vol 41 (3) ◽

pp. 323-327 ◽

Cited By ~ 52

Author(s):

K. J. Kosunen ◽

A. J. Pakarinen ◽

K. Kuoppasalmi ◽

H. Adlercreutz

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Heat Stress ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Arterial Blood ◽

Main Components ◽

Intense Heat

Plasma renin activity (PRA), angiotensin II, and aldosterone levels, arterial blood pressure, and heart rate of six male students were investigated during and after heat stress in a sauna bath. Increased PRA, angiotensin II, and aldosterone levels were found both during and after sauna. The greatest mean increases in PRA (94.9 +/- 10.4% SE, P less than 0.005) and angiotensin II (196 +/- 54.7% SE, P less than 0.02) were observed at the end of the heat stress (at 20 min), and that in plasma aldosterone (505 +/- 209% SE, P less than 0.02) 30 min after the sauna. The heart rate roughly doubled during the heat stress and there was a transient increase followed by a decrease in systolic blood pressure and a decrease in diastolic blood pressure. This study demonstrates that intense heat stress can cause remarkable changes in the three main components of the renin-angiotensin-aldosterone system.

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Acute and Chronic Effects of Nifedipine on Plasma Renin Activity and Plasma Adrenaline and Noradrenaline in Controls and Hypertensive Patients

Clinical Science ◽

10.1042/cs057115s ◽

1979 ◽

Vol 57 (s5) ◽

pp. 115s-117s ◽

Cited By ~ 38

Author(s):

L. Corea ◽

N. Miele ◽

M. Bentivoglio ◽

E. Boschetti ◽

E. Agabiti-Rosei ◽

...

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Sublingual Administration ◽

Plasma Adrenaline ◽

Hypertensive Patients ◽

Long Term Treatment ◽

Normotensive Subjects

1. Nifedipine, a calcium antagonist drug, was given sublingually (10 mg) to seven normal subjects and 19 patients with essential hypertension. In addition, 12 of the hypertensive subjects then received nifedipine (10 mg thrice daily) for 3 weeks. 2. Sublingual administration of nifedipine in hypertensive patients induced a prompt and sustained reduction of blood pressure, without a significant increase of heart rate; in normotensive subjects blood pressure did not change, and heart rate was significantly increased. After chronic treatment, blood pressure remained reduced and heart rate did not rise. 3. Plasma catecholamines and plasma renin activity increased significantly in normotensive subjects after acute administration. 4. After both acute and chronic administration, only plasma noradrenaline was significantly increased in hypertensive patients; in long-term treatment, it was increased in both the lying and standing positions. 5. Nifedipine is an active antihypertensive drug, which may induce some degree of sympathetic activation.

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Humoral Effects of the Oral Converting-Enzyme Inhibitor Sq 14 225 in Hypertensive Patients in Supine and Tilted Position

Clinical Science ◽

10.1042/cs057149s ◽

1979 ◽

Vol 57 (s5) ◽

pp. 149s-152s ◽

Cited By ~ 6

Author(s):

A. Morganti ◽

T. G. Pickering ◽

J. Lopez-Ovejero ◽

J. H. Laragh

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Nervous System ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Renin Activity ◽

Converting Enzyme ◽

Hypertensive Patients ◽

Sympathetic Nervous

1. To evaluate the effects of converting-enzyme inhibition on the sympathetic nervous system, on renin and on the other known regulators of aldosterone secretion, we measured blood pressure, heart rate, plasma noradrenaline, adrenaline, renin activity, aldosterone, cortisol and serum potassium in 15 sodium-repleted hypertensive patients in supine position and during 30 min of 65° head-up tilt before and during treatment with SQ 14 225. 2. SQ 14 225 produced significant decreases in supine blood pressure and plasma aldosterone and significant increments in plasma renin activity and potassium; in contrast, heart rate, noradrenaline, adrenaline and cortisol were unchanged. 3. While in control tilt studies blood pressure was always maintained, during treatment three of 15 patients had vasovagal syncopes. In the remaining 12 blood pressure was maintained during tilt on SQ 14 225; however, while the tilt-induced responses in heart rate and adrenaline were as in control studies, the 30 min increments in noradrenaline were significantly higher. 4. Both before and during treatment the responses of plasma renin activity and aldosterone to tilt were parallel, and correlated with each other, and cortisol and potassium changed only slightly. 5. It is concluded that the SQ 14 225-induced fall in blood pressure occurs without a concomitant rise in sympathetic nervous activity; thus the increase in supine plasma renin activity, being a reflection of the interruption of the angiotensin feedback mechanism on renin release, indicates an effective suppression of angiotensin II formation. 6. During SQ 14 225 the persistence of aldosterone response to tilt and its relationship with renin activity suggest that the enzymatic blockade is over-ridden; however, in the presence of a reduced formation of angiotensin II a more pronounced response of the sympathetic nervous system is required to defend blood pressure against postural changes.

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Effect of enalapril (MK-421), an orally active angiotensin I converting enzyme inhibitor, on blood pressure, active and inactive plasma renin, urinary prostaglandin E2, and kallikrein excretion in conscious rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y84-019 ◽

1984 ◽

Vol 62 (1) ◽

pp. 116-123 ◽

Cited By ~ 15

Author(s):

Ernesto L. Schiffrin ◽

Jolanta Gutkowska ◽

Gaétan Thibault ◽

Jacques Genest

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

Ace Inhibition ◽

Renin Activity ◽

Prostaglandin E ◽

Converting Enzyme ◽

Angiotensin I ◽

Angiotensin I Converting Enzyme

The angiotensin I converting enzyme (ACE) inhibitor enalapril (MK-421), at a dose of 1 mg/kg or more by gavage twice daily, effectively inhibited the pressor response to angiotensin I for more than 12 h and less than 24 h. Plasma renin activity (PRA) did not change after 2 or 4 days of treatment at 1 mg/kg twice daily despite effective ACE inhibition, whereas it rose significantly at 10 mg/kg twice daily. Blood pressure fell significantly and heart rate increased in rats treated with 10 mg/kg of enalapril twice daily, a response which was abolished by concomitant angiotensin II infusion. However, infusion of angiotensin II did not prevent the rise in plasma renin. Enalapril treatment did not change urinary immunorcactive prostaglandin E2 (PGE2) excretion and indomethacin did not modify plasma renin activity of enalapril-treated rats. Propranolol significantly reduced the rise in plasma renin in rats receiving enalapril. None of these findings could be explained by changes in the ratio of active and inactive renin. Water diuresis, without natriuresis and with a decrease in potassium urinary excretion, occurred with the higher dose of enalapril. Enalapril did not potentiate the elevation of PRA in two-kidney one-clip Goldblatt hypertensive rats. In conclusion, enalapril produced renin secretion, which was in part β-adrenergically mediated. The negative short feedback loop of angiotensin II and prostaglandins did not appear to be involved. A vasodilator effect, apparently independent of ACE inhibition, was found in intact conscious sodium-replete rats.

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Hypertension in Dahl salt-sensitive rats: biochemical and immunohistochemical studies

Clinical Science ◽

10.1042/cs0830013 ◽

1992 ◽

Vol 83 (1) ◽

pp. 13-22 ◽

Cited By ~ 33

Author(s):

J. Bouhnik ◽

J. P. Richoux ◽

H. Huang ◽

F. Savoie ◽

T. Baussant ◽

...

Keyword(s):

Blood Pressure ◽

Angiotensin Ii ◽

Plasma Renin Activity ◽

Plasma Renin ◽

High Salt ◽

Renin Activity ◽

Deficient Diet ◽

High Salt Diet ◽

Salt Diet ◽

Plasma Angiotensin

1. The renin-angiotensin and kinin-kallikrein systems of Dahl salt-sensitive and salt-resistant rats fed diets with different salt contents were analysed using biochemical and immunocytochemical techniques. 2. Blood pressure increased by 45% in salt-sensitive rats only, after 4 weeks on a high-salt diet. The plasma renin activity and plasma angiotensin II concentration remained at the same levels in salt-sensitive rats on the high-salt diet as on the normal salt diet, whereas the plasma renin activity and plasma angiotensin II concentration of salt-resistant rats fed the high-salt diet were lower. The plasma renin activity and the plasma angiotensin II concentration were elevated in both salt-resistant and salt-sensitive rats fed the salt-deficient diet but were much more elevated in salt-resistant than in salt-sensitive rats. 3. The kidney immunocytochemical data paralleled the data on plasma parameters. Salt-sensitive rats had fewer renin positive juxtaglomerular apparatuses than salt-resistant rats on the normal diet, and the increase on the sodium-deficient diet was also smaller in salt-sensitive rats. Salt-sensitive rats fed the high-salt diet and the standard diet had almost no angiotensin II immunoreactivity compared with the salt-resistant rats on the same diets. 4. The total renal kallikrein content of salt-sensitive rats was lower than that of salt-resistant rats on all three diets, as was the amount of kallikrein excreted in the urine on the standard and the high-salt diets. The differences resulted from a reduction in active kallikrein. The increase in kallikrein in salt-sensitive and salt-resistant rats on the salt-deficient diet was not significantly different. 5. There were similar changes in immunopositive kallikrein in the kidneys of salt-sensitive and salt-resistant rats with diet, with a large increase in kallikrein biosynthesis on the low-salt diet. The plasma concentration of high-molecular-mass kininogen was not significantly different in salt-sensitive and salt-resistant rats, but there was a significant increase in T-kininogen in salt-sensitive rats fed the high-salt diet. 6. In conclusion, the absence of decreases in the plasma renin activity and the plasma angiotensin II concentration in salt-sensitive rats fed the high-salt diet might partially explain the increase in blood pressure.

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Role of vasopressin in blood pressure regulation in conscious water-deprived dogs

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1983.244.1.r74 ◽

1983 ◽

Vol 244 (1) ◽

pp. R74-R77 ◽

Cited By ~ 3

Author(s):

J. Schwartz ◽

I. A. Reid

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Plasma Renin Activity ◽

Water Deprivation ◽

Plasma Renin ◽

Renin Activity ◽

Pressure Regulation

The role of vasopressin in the regulation of blood pressure during water deprivation was assessed in conscious dogs with two antagonists of the vasoconstrictor activity of vasopressin. In water-replete dogs, vasopressin blockade caused no significant changes in mean arterial pressure, heart rate, plasma renin activity (PRA), or plasma corticosteroid concentration. In the same dogs following 48-h water deprivation, vasopressin blockade increased heart rate from 85 +/- 6 to 134 +/- 15 beats/min (P less than 0.0001), increased cardiac output from 2.0 +/- 0.1 to 3.1 +/- 0.1 1/min (P less than 0.005), and decreased total peripheral resistance from 46.6 +/- 3.1 to 26.9 +/- 3.1 U (P less than 0.001). Plasma renin activity increased from 12.4 +/- 2.2 to 25.9 +/- 3.4 ng ANG I X ml-1 X 3 h-1 (P less than 0.0001) and plasma corticosteroid concentration increased from 3.2 +/- 0.7 to 4.9 +/- 1.2 micrograms/dl (P less than 0.05). Mean arterial pressure did not change significantly. When the same dogs were again deprived of water and pretreated with the beta-adrenoceptor antagonist propranolol, the heart rate and PRA responses to the antagonists were attenuated and mean arterial pressure decreased from 103 +/- 2 to 91 +/- 3 mmHg (P less than 0.001). These data demonstrate that vasopressin plays an important role in blood pressure regulation during water deprivation in conscious dogs.

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