Ontogeny of renal renin release in spontaneously hypertensive rat and Wistar-Kyoto rat

The role of renin-angiotensin system in generation of genetic hypertension is unclear. Renal renin secretion was examined in renal superficial cortical slices from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) at 4 wk (prehypertensive), 6 wk (early hypertensive), and 12 wk (established hypertension) of age. Basal renin release in SHR was greater at 4 wk (749 ± 55 vs. 480 ± 50 ng/mg, P < 0.005) and at 6 wk (428 ± 70 vs. 266 ± 60 ng/mg, P < 0.02). Basal renin release declined by 43% between 4 and 6 wk and by 34% between 6- and 12-wk time periods in SHR. In SHR and WKY at all ages, renin responses to stimulation with isoproterenol (ISO, 10^-5 and 10^-6 M, respectively) were similar. Angiotensin II (ANG II) resulted in a significant reduction in renin release in both SHR and WKY at 10^-7 M in all age groups. The ANG II-induced percent change in renin release from control of SHR was less compared with WKY rats at 10^-8 and 10^-9 M at 4 wk of age. When ANG II was tested in presence of β-adrenergic stimulation, a comparable renin inhibitory response was observed in both SHR and WKY. The number of ANG II-binding sites in proximal tubular brush-border membrane (BBM) was increased in SHR vs. WKY rats (458 ± 18 vs. 235 ± 12 fmol ANG II/mg BBM protein, P < 0.001) at 4 wk of age. These data document increased basal renin release and ANG II-binding sites in proximal tubular BBM in 4 wk SHR compared with age-matched WKY rat. Differences in renin secretion are abolished by 12 wk of age. A subtle defect in ANG II inhibition of intrarenal renin secretion may occur in SHR at 4 wk of age. This early increase in activity of intrarenal renin-angiotensin system may contribute to pathogenesis of genetic hypertension.