Intracellular pH: effect on pulmonary arterial smooth muscle.
To investigate the effect of changes in intracellular H+ concentration [( H+]i) on pulmonary arterial tone, isolated canine intrapulmonary arteries were exposed to NH4Cl (4-120 mM). Above 4 mM, NH4Cl caused contraction. When induced by less than or equal to 30 mM, contraction was not endothelium dependent and was unaffected by calcium-free medium or by nifedipine (10 microM). Exposure to ryanodine or norepinephrine in calcium-free medium reduced subsequent NH4Cl-induced contraction. Measurements of [H+]i and tension indicated that contraction induced by 30 mM NH4Cl occurred simultaneously with development of peak intracellular alkalosis (delta [H+]i = -47 +/- 9 nM, n = 7). Withdrawal of NH4Cl produced a rapid cytosolic acidification (delta [H+]i = + 131 +/- 29 nM, n = 7), which coincided with a transient nifedipine-sensitive contraction. In the isolated perfused rat lung, addition and removal of NH4Cl similarly increased pulmonary arterial pressure. These data suggest that intracellular alkalosis stimulates pulmonary arterial smooth muscle contraction directly and through release of calcium from intracellular sites. Intracellular acidification appears to stimulate transient contraction by allowing calcium entry from extracellular sources through voltage-activated channels. We conclude that modifications in intracellular pH effect pulmonary arterial smooth muscle tone and consequently can alter blood flow through the lung.
Krampetz
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Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46202.
Rhoades
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RA
D000643:Ammonium Chloride / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D004837:Epinephrine / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008168:Lung / Q000502:physiology*; D008297:Male; D008744:Methylamines / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D010477:Perfusion; D011189:Potassium Chloride / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology*; D011652:Pulmonary Circulation; D051381:Rats; D011919:Rats, Inbred Strains; D012433:Ryanodine / Q000494:pharmacology
D008744:Methylamines; D000643:Ammonium Chloride; D000804:Angiotensin II; D012433:Ryanodine; D011189:Potassium Chloride; C027451:methylamine; D004837:Epinephrine