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

This study tested the hypothesis that afferent arteriolar responses to purinoceptor activation are attenuated, and Ca 2+ signaling mechanisms are responsible for the blunted preglomerular vascular reactivity in angiotensin II (Ang II) hypertension. Experiments determined the effects of ATP, the P2X 1 agonist β,γ–methylene ATP or the P2Y agonist UTP on arteriolar diameter using the juxtamedullary nephron technique and on renal myocyte intracellular Ca 2+ concentration ([Ca 2+ ] i ) using single cell fluorescence microscopy. Six or 13 days of Ang II infusion significantly attenuated the vasoconstrictor responses to ATP and β,γ–methylene ATP ( P 2+ ] 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 [Ca 2+ ] i in response to β,γ–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 P2X 1 receptor–mediated signal transduction.