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(Hypertension. 2005;46:562.)
© 2005 American Heart Association, Inc.

Original Articles

Impaired Ca²⁺ Signaling Attenuates P2X Receptor–Mediated Vasoconstriction of Afferent Arterioles in Angiotensin II Hypertension

Xueying Zhao; Anthony K. Cook; Mary Field; Brentan Edwards; Shali Zhang; Zhanying Zhang; Jennifer S. Pollock; John D. Imig; Edward W. Inscho

From the Vascular Biology Center (X.Z., M.F., J.S.P., J.D.I.), Department of Physiology (A.K.C., B.E., S.Z., Z.Z., J.D.I., E.W.I.), and Department of Pharmacology and Toxicology (X.Z., J.S.P.), Medical College of Georgia, Augusta.

Correspondence to Edward W. Inscho, PhD, Department of Physiology, Medical College of Georgia, 1120 15th St, Augusta, GA 30912-3000. E-mail einscho{at}mail.mcg.edu

This study tested the hypothesis that afferent arteriolar responses to purinoceptor activation are attenuated, and Ca²⁺ signaling mechanisms are responsible for the blunted preglomerular vascular reactivity in angiotensin II (Ang II) hypertension. Experiments determined the effects of ATP, the P2X₁ agonist ß,–methylene ATP or the P2Y agonist UTP on arteriolar diameter using the juxtamedullary nephron technique and on renal myocyte intracellular Ca²⁺ concentration ([Ca²⁺]_i) using single cell fluorescence microscopy. Six or 13 days of Ang II infusion significantly attenuated the vasoconstrictor responses to ATP and ß,–methylene ATP (P<0.05). During exposure to ATP (1, 10, and 100 µmol/L), afferent diameter declined by 17±2%, 29±3%, and 30±2% in normal control rats and 8±3%, 7±3%, and 22±3% in kidneys of Ang II–infused rats (13 days). Renal myocyte intracellular calcium responses to ATP or ß,–methylene ATP were also decreased in Ang II hypertensive rats. In myocytes of control rats, peak increases in [Ca²⁺]_i averaged 107±21, 170±38, and 478±79 nmol/L at ATP concentrations of 1, 10, and 100 µmol/L, respectively. Ang II infusion for 13 days decreased the peak responses to ATP (1, 10, and 100 µmol/L) to 65±13, 102±20, and 367±73 nmol/L, respectively. The peak increases in [Ca²⁺]_i in response to ß,–methylene ATP were also reduced in Ang II hypertensive rats. However, angiotensin hypertension did not change the UTP-mediated vasoconstrictor responses or the myocyte calcium responses to UTP. These results indicate that the impaired autoregulatory response observed in Ang II–dependent hypertension can be attributed to impairment of P2X₁ receptor–mediated signal transduction.

Key Words: autoregulation • receptors, purinergic • calcium • microcirculation • renal circulation

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