Age-dependent regulation of renal vasopressin V1A and V2 receptors in rats with genetic hypertension: implications for the treatment of hypertension

Abstract

The role of arginine vasopressin (AVP) as a hypertensive hormone remains controversial. We have previously reported that intervention with a V1A receptor antagonist in 6-week-old prehypertensive spontaneously hypertensive rats (SHR) for 4 weeks attenuated the subsequent development of hypertension in adult SHR. This study assessed the age-dependent regulation of plasma AVP levels and kidney V1A and V2 receptor expression during the development of hypertension in SHR and in normotensive Sprague Dawley rats. Systolic blood pressure (SBP), plasma AVP, and plasma renin activity (PRA) and kidney V1A and V2 receptor expression were assessed. SHR were studied at three ages: prehypertensive (6 weeks), developed hypertension (10 weeks), and established hypertension (16 weeks). SBP increased with age in SHR (P < .01) and both plasma AVP (P < .01) and PRA (P < .05) were increased in 10-week-old SHR. Renal medulla V1A receptor gene expression decreased in 10-week and 16-week-old SHR (P < .01), with a reduction in V1A receptor protein in the inner medulla of 16-week-old SHR (P < .05) compared with young SHR. There was no change in V2 receptor expression during the development of hypertension. In normotensive rats, plasma AVP, PRA, and kidney V1A and V2 receptor expression were unchanged over time. These data suggest that in SHR, activation of plasma AVP and the renal V1A receptor occurs during developing hypertension, with downregulation when hypertension is established. The use of V1A receptor antagonists in prehypertension may provide a unique opportunity for the prevention of hypertension in high-risk individuals.