Age-dependent regulation of vasopressin V_1areceptors in preglomerular vessels from the spontaneously hypertensive rat

Abstract

Experiments were performed to get insight into the role of AVP receptor V(1a) regulation with age, i.e., during development and maintenance of high blood pressure. Previous studies showed an increased gene expression and renal vascular response to AVP in young spontaneously hypertensive rats (SHR). The age regulation of the V(1a) receptor was examined in preglomerular vessels from 5-, 10-, 20-, and 70-wk-old SHR using normotensive Wistar-Kyoto rats (WKY) as controls. Real-time PCR and ligand binding were used for analysis of receptor expression, and the change in cytosolic calcium concentration during stimulation of isolated preglomerular vessels with AVP was studied. Studies showed an increase of the V(1a) receptor protein and mRNA from 5-and 10-wk-old SHR compared with vessels from 20- and 70-wk-old SHR. In 5-wk-old SHR receptor density was 84 +/- 13 fmol/mg protein, and 38 +/- 11 fmol/mg protein in 70-wk-old SHR (P < 0.05). mRNA in the 5- and 70-wk-old SHR was 15,854 +/- 629 and 3,181 +/- 224 V(1a) mRNA/108 18S ribosomal RNA, respectively (P < 0.001). Values from WKY at all ages were similar to 20- and 70-wk-old SHR. During stimulation with AVP, the change in cytosolic calcium in vessels from 5-wk-old SHR increased 234 +/- 59 nM, whereas the increase was 89 +/- 9 nM in 70-wk-old SHR (P = 0.03). These results indicate that the V(1a) receptor is increased at protein and mRNA level during development of hypertension in SHR but is normalized when hypertension is established.

Enhanced response to AVP in the interlobular artery from the spontaneously hypertensive rat

“…In a recent paper, we observed greater variations in the Ca i 2ϩ response in isolated preglomerular fragments from young SHR compared with age-matched WKY, and we decided to explore this observation further (39). In the present study, we found a nearly twofold increased calcium response in ILA compared with AA in SHR.…”

“…The increased V 1a receptor density in hypertensive compared with normotensive animals was seen only at the age of 5 to 10 wk, which is the period when SHR develop hypertension (39). This suggests that the density of V 1a receptors in the renal vascular tree might be of importance for the development of hypertension in SHR.…”

Vasopressin antagonists in polycystic kidney disease

“…Vasopressin regulates the expression of beta and gamma subunits of ENaC in collecting ducts of Sabra rats [21]. Up-regulation of V1a receptors in preglomerular vessels [22] and of V2 receptors [23] in collecting ducts is thought to play a role in the development of hypertension in the SHR. The relevance of these observations to ADPKD-associated hypertension, which exhibits many features of salt-sensitive hypertension, deserves consideration.…”

Enhanced Ca2+response to AVP in preglomerular vessels from rats with genetic hypertension during different hydration states

“…The elevated number of renal V 1a receptors in SHR afferent arterioles at 8 wk of age decreases to the level seen in WKY at 20 wk of age (49,50). In contrast, the density of renal vascular V 1a receptor is stable throughout life in WKY both at the protein and mRNA levels (49). Other investigators report an equal expression level of V 1a receptors in adult WKY and SHR using Western blotting in renal microvessels (17).…”

“…These findings can account for the increased renal vascular reactivity to AVP observed in vivo and in vitro findings of enhanced calcium signaling in preglomerular arterioles and individual VSMC (13,14,16,22). The increased V 1a receptor density in renal resistance vessels of young euvolemic SHR contrasts with a normal density of ANG II AT 1 receptors (6) and with the normalization of V 1a receptors between Wistar-Kyoto rats (WKY) and SHR by the age of 20 wk (49).…”