title: Extracellular acidosis contracts coronary but neither renal nor mesenteric artery via modulation of H+,K+-ATPase, voltage-gated K+ channels and L-type Ca2+ channels.
abstract: Extracellular acidosis (EA) jeopardizes the heart, whereas mild extracellular alkalinization is cardioprotective, but it remains elusive how the coronary artery (CA) responses to EA. In the present study, EA was demonstrated to induce contraction in rat coronary artery (RCA) in a manner dependent on extracellular pH (pHo, 7.2-6.6), whereas it did not affect the resting tone of either rat renal interlobe artery (RIA) or mesenteric artery (MA). The amplitude of contraction provoked by pHo 6.8 was approximately equal to that induced by 60 mmol l(-1) KCl at pHo 7.4. Blockade of L-type voltage-gated Ca(2+) channels and inhibition of H(+),K(+)-ATPase attenuated the contraction, whereas inhibition of nitric oxide synthesis and endothelial denudation augmented it. A molecular probe study showed that EA acidified the cytosol of arterial smooth muscle cells (ASMCs) in RIA and MA, but alkalinized it in RCA. Extracellular acidosis elevated the intracellular Ca(2+) concentration exclusively in RCA ASMCs. Patch-clamp studies showed that EA enhanced L-type voltage-gated Ca(2+) channel currents in RCA ASMCs, but depressed the currents in MA ASMCs and did not affect the currents in RIA ASMCs. Extracellular acidosis depressed voltage-gated K(+) channel (KV) currents only in RCA ASMCs. Lansoprazole blunted all these observed effects of EA on RCA. Taken together, the present results demonstrate that the responses of RCA to EA are different from those of RIA and MA and suggest that activation of L-type voltage-gated Ca(2+) channels and H(+),K(+)-ATPase as well as depression of KV may, at least partly, underlie the EA-induced contraction in RCA.
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China Medical Functional Experimental Center, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Longgang
authors.initials: L
authors.lastname: Niu
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Hou
authors.affiliation: Medical Functional Experimental Center, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Cui
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China.
authors.forename: Xuanping
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China Medical Functional Experimental Center, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China Cardiovascular Division of Physiology Department, Shanxi Medical University, Xinjiannanlu 56, Taiyuan, 030001, Shanxi Province, China zmspharmacol@sina.com.
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Zhang
mesh_terms: D000138:Acidosis / Q000503:physiopathology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects; D003331:Coronary Vessels / Q000503:physiopathology*; D003600:Cytosol / Q000378:metabolism; D017506:H(+)-K(+)-Exchanging ATPase / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D064747:Lansoprazole / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000503:physiopathology; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated / Q000187:drug effects; D017208:Rats, Wistar; D012077:Renal Artery / Q000503:physiopathology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D024642:Potassium Channels, Voltage-Gated; D064747:Lansoprazole; D017506:H(+)-K(+)-Exchanging ATPase