P2X1 receptor-mediated vasoconstriction of afferent arterioles in angiotensin II-infused hypertensive rats fed a high-salt diet.

ABSTRACT: Experiments tested the hypothesis that P2 receptor reactivity is impaired in angiotensin (Ang) II hypertensive rats fed an 8%NaCl diet (Ang II+HS). Juxtamedullary afferent arteriolar autoregulatory behavior was determined over a pressure range of 65 to 200 mm Hg. Arteriolar responsiveness to P2X1 (?,?-methylene ATP) or P2Y2 receptor (uridine triphosphate) activation was determined in vitro. Systolic blood pressure averaged 126±3 and 225±4 mm Hg in control and Ang II+HS rats, respectively (P<0.05). In control kidneys, ?,?-methylene ATP (10(-8) to 10(-4) mol/L) reduced arteriolar diameter by 8±3%, 13±5%, 19±5%, 22±6%, and 24±9%, respectively, whereas uridine triphosphate reduced diameter by 2±1%, 2±2%, 9±3%, 37±7%, and 58±7%. Autoregulation was markedly blunted in Ang II+HS kidneys, with arteriolar diameter remaining essentially unchanged when perfusion pressure increased to 200 mm Hg compared with a 40±2% decline in diameter observed in normal kidneys over the same pressure range (P<0.05). P2X1 receptor-mediated vasoconstriction was significantly attenuated in Ang II+HS kidneys. ?,?-Methylene ATP reduced arteriolar diameter by 1±1%, 3±2%, 6±1%, 9±3%, and 7±1%, respectively (P<0.05), versus control rats. Similar patterns were noted when hypertensive perfusion pressures were used. Uridine triphosphate-mediated responses were unchanged in Ang II+HS rats compared with control, indicating preservation of P2Y2 receptor function. Ang II+HS blunted P2X1-mediated increases in intracellular Ca2+ concentration in preglomerular smooth muscle cells. Therefore, Ang II+HS rats exhibit attenuated afferent arteriolar responses to P2X1 receptor stimulation. These data support the hypothesis that P2X1 receptors are important for pressure-mediated autoregulatory responses. Impairment of P2X1 receptor function may explain the hypertension-induced decline in renal autoregulatory capability.

SUBMITTER: Inscho EW 

PROVIDER: S-EPMC3060280 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature