Effects of indomethacin on systemic and renal haemodynamics in conscious lambs

Kesavarao Kumar Ebenzar, Fatemeh Sharbef Ghane and Francine Gabriel Smith

Department of physiology & Biophysics, Faculty of Medicine, University of Calgary, Calgary, Alberta T2N 4N1, Canada

Both prostaglandins (PGs) PGE₂ and PGI₂ can act as renal vasodilators, these effects being exacerbated when the rennin-angiotensin system is activated. Therefore, we hypothesized that PGs would play more predominant role in modulating renal haemodynamics in the newborn period, when the rennin-angiotensin system is activated. To this end, the role of endogenously produced PGs in modulating systemic and renal haemodynamics was investigated in two groups of conscious lambs aged~1 and~6 weeks. Arterial pressure, venous pressure and renal blood flow were measured for 5 min before (control) and for 20 min after intravenous injection of vehicle (experiment 1).Twenty-four hours later, this protocol was repeated with intravenous injection of the non-selective cyclo-oxygenase inhibitor indomethacin (1 mg kg^-1, experiment 2). Heart rate was calculated from the systolic peak of the arterial pressure waveform, and renal vascular resistance (RVR) was calculated from the measured variables. In response to indomethacin but not vehicle, in both age groups of lambs there was an increase in mean arterial pressure and pulse interval, as well as a marked increase in RVR. These responses to indomethacin were, however, transient, with baseline levels being resumed within minutes . Although the hypothesis that PGs play a greater role in modulating renal haemodynamics early in life is not supported, these data do provide evidence that endogenously produced PGs modulate systemic and renal haemodynamics during postnatal maturation . It is apparent, however, that other vasoactive factors must be rapidly recruited in order to the circulatory responses to removal of vasodilatory PGs in the developing newborn.