Kappa opioids modulate the arterial baroreflex control of heart rate in conscious young sheep

The present study tested the hypothesis that kappa-opioids modulate the arterial baroreflex control of heart rate in conscious young sheep. Various parameters governing the arterial baroreflex control of heart rate were assessed before and after activation of kappa-opiate receptors (KOR) by i.v. administration of the specific KOR agonist U-50488H (experiment 1) or vehicle (experiment 2) to conscious, chronically instrumented lambs aged 42 +/- 2 days (n = 6). The 2 experiments were administered in random order at minimum intervals of 48 h. Thirty min after U-50488H treatment, there was an increase in diastolic and mean arterial pressure and in heart rate, returning to control levels by 90 min. A significant increase in the arterial pressure at the midpoint of the baroreflex range and in the minimum heart rate as well as a significant decrease in the heart rate range over which the arterial baroreflex operates were also seen at 30 min after U-50488H, gradually returning to control levels over 120 min. Vehicle had no effect on any of the parameters governing the arterial baroreflex control of heart rate. These data provide the first direct evidence that under physiological conditions in young lambs, the arterial baroreflex control of heart rate is altered after administration of the specific KOR agonist U-50488H, revealing a previously unidentified role for this opioid receptor.