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

Abstract

Exaggerated arginine vasopressin (AVP)-induced calcium signaling and renal vasoconstriction, characteristic in young spontaneously hypertensive rats (SHR) during euvolemia, are related to greater amounts of V1areceptor mRNA and V1aprotein in preglomerular resistance arterioles. The present study determined whether V1areceptor density and calcium signal transduction in the renal vasculature of young SHR is regulated appropriately during physiological changes in hydration state. [3H]AVP ligand binding documented two- to threefold greater density of V1areceptors in euvolemic SHR vs. Wistar-Kyoto (WKY) rats. Parallel changes in V1areceptor density were observed in both strains during chronic water loading (plus ∼50 fmol/mg) and during dehydration (minus ∼50 fmol/mg). Affinity was unchanged. Real-time RT-PCR demonstrated that V1amRNA in preglomerular arterioles was three times greater in euvolemic SHR. Dehydration decreased expression ∼50% in renal vessels independent of rat strain; water loading increased V1amRNA. Thus V1areceptor regulation correlated with changes in mRNA in a normal manner in response to chronic changes in AVP concentration, albeit set at a higher level in SHR. In dehydrated animals, AVP increased the cytosolic Ca2+concentration ([Ca2+]i) by 60 ± 5 and 112 ± 13 nM cytosolic Ca2+in WKY and SHR, respectively ( P < 0.01), whereas in hydrated animals the [Ca2+]iincrease was 168 ± 10 and 220 ± 18 nM, respectively ( P < 0.05). In all hydration states, calcium signaling was greater in SHR compared with WKY ( P < 0.05). Calcium signaling paralleled changes in the receptor density and mRNA. Mechanisms other than hydration state per se are likely to be responsible for the two- to threefold difference in the V1areceptor density between WKY and SHR in the renal vasculature at the critical age of 6 wk.