Effects of intracellular alkalinization on resting and agonist-induced vascular tone.
To evaluate the influence of intracellular alkalinization on basal and agonist-induced vascular tone, we studied the effect of NH4Cl on rat aorta. NH4Cl induced a gradually developing contraction in a dose-dependent manner. Although the contractile response to 20 mM NH4Cl was associated with a latent period (LP) of 23.4 +/- 2.8 min, intracellular pH (pHi) measurements in cultured rat aortic smooth muscle cells showed that NH4Cl-induced intracellular alkalinization was immediate and transient, returning to basal pHi levels in about 30-35 min. Agents that elevate Ca2+, such as A23187 and high KCl, significantly reduced the LP associated with 20 mM NH4Cl-induced contraction. NH4Cl-induced contractions were sensitive to extracellular Ca2+ removal and to the addition of forskolin (1 microM); however, NH4Cl by itself did not cause Ca2+-influx as shown by 45Ca-uptake studies. Addition of 20 mM NH4Cl to precontracted tissues resulted in a transient relaxation, which was complete in approximately 10 min, followed by a contraction above the original level of tone. NH4Cl pretreatment caused time-dependent alterations in both the rapid and slow phases of phenylephrine and angiotensin II contractions. Rapid-phase of phenylephrine and angiotensin II contractions. Rapid-phase responses were diminished at shorter NH4Cl incubation times (10 min), whereas slow-phase response was augmented after a longer incubation (20 min). Overall, the vasorelaxant and vasoconstrictor effects induced by NH4Cl suggest a complex relationship between intracellular alkalinization and arterial contractility.
Danthuluri
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Section of Pharmacology, College of Pharmacy and Allied Health Professions, Northeastern University, Boston, Massachusetts 02115.
Deth
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RC
D000085:Acetates / Q000494:pharmacology; D000643:Ammonium Chloride / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008955:Models, Cardiovascular; D009119:Muscle Contraction / Q000187:drug effects; D009129:Muscle Tonus / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012016:Reference Values
D000085:Acetates; D000643:Ammonium Chloride; D000804:Angiotensin II; D005576:Colforsin; D000001:Calcimycin; D004533:Egtazic Acid; D002794:Choline; D002118:Calcium