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

1. 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-1, then 0.12 mg kg-1 min-1), 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.