Ontogeny of renal hemodynamic response to terbutaline and forskolin in sheep

KT Nakamura, BM Alden, GP Matherne, PA Jose and JE Robillard

Department of Pediatrics, University of Iowa College of Medicine, Iowa City.

The renal hemodynamic response to renal arterial infusions of terbutaline and forskolin were compared in chronically instrumented fetal (129-139 days gestation; term 145 days), newborn (7-14 days old) and nonpregnant adult sheep. Infusions of terbutaline produced renal vasodilation in all age groups with maximal increases being higher in fetal (47 +/- 7%) than in newborn (30 +/- 8%) or adult sheep (24 +/- 5%). Terbutaline-mediated renal vasodilation was inhibited by the selective beta 2 adrenoceptor antagonist, ICI 118,551, whereas infusion of selective beta 1 adrenoceptor antagonist, ICI 89,406, had no effect. Moreover, terbutaline effects were unchanged after phentolamine infusion to inhibit potential antagonistic effects of neuronal norepinephrine release by presynaptic beta 2 adrenoceptor stimulation. Renal arterial infusion of forskolin produced renal vasodilation of similar magnitude in all age groups, with maximal increases of 46 +/- 5, 38 +/- 3 and 38 +/- 5% in fetal, newborn and adult sheep, respectively. Taken together, these results suggest that renal vasodilatory mechanisms stimulated by selective activation of beta 2 adrenoceptors (terbutaline) are greater during fetal life. However, direct activation of adenylate cyclase with forskolin produces essentially similar renal vasodilatory responses during development in sheep. Thus, reasons to explain age-dependent differences in renal vasodilation observed previously with endogenous catecholamines may be at the receptor-hormone level.

Volume 247, Issue 2, pp. 453-459, 11/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics