Impaired Ca2+ signaling attenuates P2X receptor-mediated vasoconstriction of afferent arterioles in angiotensin II hypertension. Hypertension 2005 Sep;46(3):562-8
Date
08/24/2005Pubmed ID
16116048DOI
10.1161/01.HYP.0000179584.39937.41Scopus ID
2-s2.0-25444437790 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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 beta,gamma-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 beta,gamma-methylene ATP (P<0.05). During exposure to ATP (1, 10, and 100 micromol/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 beta,gamma-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 micromol/L, respectively. Ang II infusion for 13 days decreased the peak responses to ATP (1, 10, and 100 micromol/L) to 65+/-13, 102+/-20, and 367+/-73 nmol/L, respectively. The peak increases in [Ca2+]i in response to beta,gamma-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.
Author List
Zhao X, Cook AK, Field M, Edwards B, Zhang S, Zhang Z, Pollock JS, Imig JD, Inscho EWMESH terms used to index this publication - Major topics in bold
AdenosineAdenosine Triphosphate
Angiotensin II
Animals
Arterioles
Blood Pressure
Calcium
Calcium Signaling
Homeostasis
Hypertension
Intracellular Membranes
Kidney
Male
Microcirculation
Muscle, Smooth, Vascular
Myocytes, Smooth Muscle
Purinergic P2 Receptor Agonists
Rats
Rats, Sprague-Dawley
Receptor, Adenosine A1
Receptors, Purinergic P2
Receptors, Purinergic P2X
Uridine Triphosphate
Vasoconstriction