Effect of prepuberal gonadectomy upon aldosterone levels in female and male SHR: interaction between blood pressure and kallikrein kinin system.

It has been suggested that an abnormal activity of the hypothalamic-pituitary-adrenal-gonadal axis may be implicated in the pathogenesis of spontaneously hypertensive rats (SHR) blood pressure hypertension. However, it is widely known that the kallikrein-kinin system plays a role in blood pressure regulation in this strain, because an inverse relation between blood pressure and urinary kallikrein excretion has been reported. It was of our interest to study how early suppression of sexual hormones affected blood pressure regulation in SHR and urinary kallikrein excretion and to elucidate the involved mechanisms. For these purpose, SH and Wistar-Kyoto (WKY) rats blood pressure, renal function, and hormonal profile were studied after prepuberal gonadectomy starting at 4 weeks of age throughout until the 12th week of age. Results were compared with those of untreated SH and WKY rats of either sex. The response to blocking agents against aldosterone and kallikrein-kinin system also were evaluated. Systolic blood pressure increased progressively in male and female SHR 12 weeks of age. Systolic blood pressure was higher in male than in female SHR, but urinary kallikrein was lower in male SHR. Prepuberal gonadectomy induced a significant decrease in systolic blood pressure in male and in female SHR at 12 weeks of age, accompanied by an increase in urinary kallikrein in male and in female SHR. Plasma aldosterone increased markedly in female and male SHR after gonadectomy. No concurrent changes in plasma renin activity or corticosterone levels were observed. The aldosterone receptor antagonist and the kallikrein inhibitor treatment blunted the blood pressure lowering effect of gonadectomy and diminished urinary kallikrein excretion. Results support the existence of a sexual dimorphism related to hypertension and urinary kallikrein and suggest an interaction among the kallikrein-kinin system, sexual hormones, and mineralocorticoids in the neonatal programming of hypertension.