P2X1 Receptor-Mediated Vasoconstriction of Afferent Arterioles in Ang II-infused Hypertensive Rats Fed a High Salt Diet

摘要

Experiments tested the hypothesis that P2 receptor reactivity is impaired in Angiotensin II hypertensive rats fed an 8% NaCl diet (AngII+HS). Juxtamedullary afferent arteriolar autoregulatory behavior was determined over a pressure range of 65 to 200mmHg. Arteriolar responsiveness to P2X1 (β, γ-methylene ATP), or P2Y2 receptor (uridine triphosphate) activation were determined, in vitro. Systolic blood pressure averaged 126±3 mmHg and 225±4 mmHg in control and AngII+HS rats, respectively (P<0.05). In control kidneys, β, γ-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 AngII+HS kidneys, with arteriolar diameter remaining essentially unchanged when perfusion pressure increased to 200mmHg, compared to 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 AngII+HS kidneys. β, γ-methylene ATP reduced arteriolar diameter by 1±1, 3±2, 6±1, 9±3 and 7±1%, respectively (P<0.05) vs. control rats. Similar patterns were noted when hypertensive perfusion pressures were used. Uridine triphosphate-mediated responses were unchanged in AngII+HS rats compared to control, indicating preservation of P2Y2 receptor function. AngII+HS blunted P2X1-mediated increases in intracellular Ca²⁺ concentration in preglomerular smooth muscle cells. Therefore, AngII+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.