title: Mechanisms of pHi control and relationships between tension and pHi in human subcutaneous small arteries.
abstract: Intracellular pH (pHi) control and relationships between pHi and tension have been investigated in human subcutaneous small arteries. Isometric tension and pHi (using 2',7'-bis(carboxyethyl)- 5(6)-carboxyfluorescein) were estimated simultaneously. pHi recovery from an acute acid load was dependent on external Na+ and partially inhibited by the absence of HCO3(-) [N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES)-buffered solution] or by the anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS). In an HCO3(-)-buffered physiological salt solution (PSS), pHi recovery was partially blocked by hexamethylene amiloride (HMA), an inhibitor of Na+/H+ exchange, and completely blocked by DIDS and HMA together. Intracellular Cl- depletion of arteries did not affect the rate of pHi recovery in PSS from an acid load. pHi recovery from acute alkalosis was unaffected by external Na+ removal, reduced in HEPES buffer, and abolished by removal of external Cl-. These data suggest that human small arteries maintain pHi by Na+/H+ exchange and Na(+)-dependent HCO3(-) exchange in response to an acid load, and Na(+)-independent Cl-/HCO3(-) exchange to counteract intracellular alkalosis. Norepinephrine (NE)-, endothelin-1 (ET-1)-, arginine vasopressin (AVP)-, and K(+)-induced tension did not alter pHi in PSS, but there was a small fall with angiotensin II (ANG II). In HEPES, stimulation with K+, NE, ANG II, or AVP led to a fall in pHi, but this did not occur with ET-1. It is therefore unlikely in vivo that an increase in pHi in these arteries would be involved in either tension development or growth induced by these agonists.
authors.affiliation: Department of Medicine, United Medical and Dental School, St. Thomas' Hospital, London, United Kingdom.
authors.forename: P
authors.initials: P
authors.lastname: Carr
authors.forename: W
authors.initials: W
authors.lastname: McKinnon
authors.forename: L
authors.initials: L
authors.lastname: Poston
mesh_terms: D000085:Acetates / Q000494:pharmacology; D019342:Acetic Acid; D000328:Adult; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000494:pharmacology; D001158:Arteries / Q000502:physiology; D001639:Bicarbonates / Q000494:pharmacology; D016232:Endothelins / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009119:Muscle Contraction / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D012867:Skin / Q000098:blood supply*; D012964:Sodium / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D000085:Acetates; D001639:Bicarbonates; D016232:Endothelins; D017923:Sodium-Hydrogen Exchangers; D000643:Ammonium Chloride; D000804:Angiotensin II; D001127:Arginine Vasopressin; C057360:5-(N,N-hexamethylene)amiloride; D000584:Amiloride; D012964:Sodium; D019342:Acetic Acid; D009638:Norepinephrine