4.7 Article

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

Journal

HYPERTENSION
Volume 57, Issue 4, Pages 780-+

Publisher

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/HYPERTENSIONAHA.110.168955

Keywords

P2 receptors; Ang II hypertension; Ca2+ signaling; autoregulation; UTP; ATP; adenosine

Funding

  1. National Institutes of Health [DK 44628, HL 074167, HL095499]

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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 P2X(1) (beta,gamma-methylene ATP) or P2Y(2) 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, beta,gamma-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). P2X(1) receptor-mediated vasoconstriction was significantly attenuated in Ang II+HS kidneys. beta,gamma-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 P2Y(2) receptor function. Ang II+HS blunted P2X(1)-mediated increases in intracellular Ca2+ concentration in preglomerular smooth muscle cells. Therefore, Ang II+HS rats exhibit attenuated afferent arteriolar responses to P2X(1) receptor stimulation. These data support the hypothesis that P2X(1) receptors are important for pressure-mediated autoregulatory responses. Impairment of P2X(1) receptor function may explain the hypertension-induced decline in renal autoregulatory capability. (Hypertension. 2011;57:780-787.)

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