Systemic and renal haemodynamic effects of the specific kappa opioid receptor agonist, U50488H, during postnatal maturation in conscious lambs

Abstract

The present experiments were carried out to investigate the role of κ-opioids in modulating systemic and renal haemodynamics in conscious, chronically instrumented lambs aged ~one week (n = 10) and six weeks (n = 15). Mean arterial pressure (MAP), mean venous pressure (MVP) and renal blood flow (RBF) were measured for 30 min before (Control) and for 90 min after I.V. administration of U50488H (EC100 dose, experiment one) or vehicle (experiment two). Heart rate (HR) was calculated from the systolic peaks of the arterial pressure waveforms; renal vascular resistance (RVR) was calculated as (MAP - MVP)/RBF. Responses to U50488H were also tested at 1, 24, 48, 72, and 96 h after administration of the selective κ-opioid receptor antagonist, GNTI. In one week old lambs, 20 min after administration of U50488H, MAP decreased from 79±4 to 74±3 mmHg, remaining at the same level for the next 30 min. In contrast, at six weeks, MAP increased by 10 min after U50488H from 80±6 to 86±9 mmHg, returning to control by 20 min. There was a marked increase in HR after U50488H from 206±26 to 243±15 and from 126±15 to 169±32 bpm, at one and six weeks, respectively; HR remained elevated for the duration of the experiment in both age groups. These responses to U50488H were abolished by GNTI at 24 – 96 h but not 1 h. There were no significant effects on RVR or RBF after U50488H, before or after GNTI, and no effects of vehicle on any of the measured or calculated variables. These data demonstrate that κ-opioids modulate resting systemic but not renal haemodynamics early in life, in an age-dependent manner. Funded by the Canadian Institutes for Health Research.