EFFECTS OF HYPOXIA ON RENIN SECRETION AND RENAL RENIN GENE-EXPRESSION

Plasma renin activity (PRA) and renal renin mRNA levels were measured in male rats exposed to hypoxia (8% O-2) or to carbon monoxide (CO; 0. 1%) for six hours. PRA increased fourfold and 3.3-fold, and renin mRNA levels increased to 220% and 200% of control, respectively. In primar y cultures of renal juxtaglomerular (JG) cells, hypoxia (lowering medi um O-2 from 20% to 3% or 1%) for 6 or 20 hours did not affect renin se cretion or gene expression. Renal denervation did not prevent stimulat ion of the renin system by hypoxia. Because norepinephrine increased 1 .7-fold and 3.2-fold and plasma epinephrine increased 3.9-fold and 7.8 -fold during hypoxia and CO inhalation, respectively, circulating cate cholamines might mediate the stimulatory effects of hypoxia on renin s ecretion and renin gene expression. Stimulation of beta-adrenergic rec eptors by continuous infusion of 160 mu g/kg/hr isoproterenol increase d PRA 17-fold and 20-fold after three and six hours, respectively, and renin mRNA by 130% after six hours. In rats with a stimulated renin s ystem (low-sodium diet), isoproterenol did not stimulate PRA or renal renin mRNA further. In summary, both arterial and venous hypoxia can s timulate renin secretion and renin gene expression powerfully in vivo but not in vitro. These effects seem not to be mediated by renal nerve s or by a direct effect on JG cells but might be mediated by circulati ng catecholamines.