title: P2X1 receptor-mediated vasoconstriction of afferent arterioles in angiotensin II-infused hypertensive rats fed a high-salt diet.
abstract: 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 P2X1 (β,γ-methylene ATP) or P2Y2 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, 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 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). P2X1 receptor-mediated vasoconstriction was significantly attenuated in Ang II+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), 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 P2Y2 receptor function. Ang II+HS blunted P2X1-mediated increases in intracellular Ca2+ concentration in preglomerular smooth muscle cells. Therefore, Ang II+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.
authors.affiliation: Department of Physiology, Georgia Health Sciences University, 1120 15th St, Augusta, GA 30912-3000, USA. einscho@georgiahealth.edu
authors.forename: Edward W
authors.initials: EW
authors.lastname: Inscho
authors.forename: Anthony K
authors.initials: AK
authors.lastname: Cook
authors.forename: Andrea
authors.initials: A
authors.lastname: Clarke
authors.forename: Shali
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhengrong
authors.initials: Z
authors.lastname: Guan
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D058474:Receptors, Purinergic P2X1 / Q000378:metabolism*; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D012982:Sodium, Dietary; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D058474:Receptors, Purinergic P2X1; D012982:Sodium, Dietary; D000804:Angiotensin II