Influence of endogenous opiates and cardiac afferents on renal nerve activity during haemorrhage in conscious rabbits.

Abstract

SUMMARY1. We investigated the effects of the opiate antagonist naloxone on changes in renal nerve activity and the renal sympathetic baroreflex during haemorrhage and whether they could be mimicked by blocking afferent input from cardiac receptors.2. Renal nerve activity, arterial pressure and heart rate were recorded in conscious rabbits during blood loss of either 18 or 34-40 % of the blood volume. The renal sympathetic baroreflex was elicited by perivascular balloon-induced changes in arterial pressure, before and at the end of haemorrhage. The experiment was repeated during intravenous naloxone infusion (4 mg kg-', then 0X12 mg kg-' min-'), and after blocking afferent input from cardiac receptors (5 % intra-pericardial procaine).3. Moderate haemorrhage elicited a rise in renal nerve activity and modest inhibition of the range of the renal sympathetic baroreflex. Severe haemorrhage triggered an abrupt fall in nerve activity and arterial pressure which was accompanied by strong inhibition of the baroreflex range and other curve parameters. There were minimal changes in the baroreceptor-heart rate reflex.4. Intravenous naloxone and pericardial procaine prevented the falls in renal nerve activity and pressure triggered by severe blood loss but did not affect the increase in activity elicited by moderate haemorrhage. Both drugs produced similar enhancement of the normovolaemic renal sympathetic baroreflex. Naloxone prevented the baroreflex inhibition elicited by both levels of haemorrhage while pericardial procaine prevented most (but not all) of the baroreflex inhibition seen during severe haemorrhage without affecting that found during moderate haemorrhage.5. We conclude that cardiac receptors (probably ventricular baroreceptors) but not arterial baroreceptors have an opiate synapse on their reflex pathways to the renal nerve. A major part of the action of naloxone during haemorrhage can be explained by blockade of this type of synapse on baroreflex pathways to renal and probably other sympathetic vasoconstrictors. The presence of procaine-resistant but naloxone-sensitive effects during haemorrhage suggests a role for extra-cardiac baroreceptors with opioid central nervous connections.

Naloxone potentiates cardiopulmonary baroreflex sympathetic control in normal humans.

“…[7][8][9][10][11][12] In humans, the arterial baroreflex control of heart rate during arterial baroreceptor deactivation with nitroprusside is potentiated by naloxone.13 Deactivation of cardiopulmonary baroreceptors during nonhypotensive hemorrhage has been shown to increase the secretion of adrenocorticotropic hormone (ACTH) in animals. '4"15 ,3-Endorphins, which have high affinity for ,u opioid receptors, are known to be released concomitantly and in equimolar concentrations with ACTH from the pituitary.…”

The effects of naloxone on the cardiovascular and respiratory effects of centrally administered corticotrophin releasing factor in conscious rabbits

“…The tachycardia was reduced by naloxone suggesting that this response to CRF may be mediated partly be opioid peptides, but these studies give no indication of the mechanism involved. An action on baroreflexes is unlikely as naloxone does not alter sensitivity in normovolaemic rabbits (Burke & Dorwood, 1988), although further studies are required to exclude an effect in the presence of CRF.…”

Chemosensitive cardiopulmonary afferents and the haemodynamic response to simulated haemorrhage in conscious rabbits

“…Whereas cardiac afferents in rabbits (Burke & Dorward, 1988;Evans et al, 1989a), and vagal afferents in rats (Skoog et al, 1985), convey the signal responsible for the sympathoinhibitory phase of haemorrhage or simulated haemorrhage, NS in dogs this signal does not appear to travel in cardiac afferents , and in primates the source of the signal is unknown (see Schadt . In rabbits (Evans et al, 1990a) and rats (Willette et al, 1982) phenylbiguanide-sensitive cardiopulmonary afferents are prominent, whereas they appear to be absent in dogs (Dawes et al, 1952) and man (Jain et al, 1972).…”

“…When about 30% of blood volume has been withdrawn (Schadt et al, 1984;Burke & Dorward, 1988;Ludbrook & Rutter, 1988), or when cardiac output has fallen by about 50% (Evans et al, 1989a, b), a second phase begins in which there is an abrupt decrease in sympathetic activity, peripheral resistance and mean arterial pressure. This sympathoinhibition is initiated by a signal from the heart (Burke & Dorward, 1988;Evans et al, 1989a) and depends on activation of a 6-opioid receptor mechanism within the central nervous system (Evans et al, 1989b). The sympathoinhibition of Phase 2 can also be prevented by injecting a specific p-opioid receptor agonist into the 4th ventricle (Evans & Ludbrook, 1990).…”

“…The maintenance of blood pressure is associated with a progressive rise in sympathetic drive (Burke & Dorward, 1988;Morita et al, 1988) and plasma noradrenaline concentration (Schadt & Gaddis, 1985), so that this first phase can be described as sympathoexcitatory. When about 30% of blood volume has been withdrawn (Schadt et al, 1984;Burke & Dorward, 1988;Ludbrook & Rutter, 1988), or when cardiac output has fallen by about 50% (Evans et al, 1989a, b), a second phase begins in which there is an abrupt decrease in sympathetic activity, peripheral resistance and mean arterial pressure. This sympathoinhibition is initiated by a signal from the heart (Burke & Dorward, 1988;Evans et al, 1989a) and depends on activation of a 6-opioid receptor mechanism within the central nervous system (Evans et al, 1989b).…”