The mechanism of acidic pH-induced contraction in aortae from SHR and WKY rats enhanced by increasing blood pressure.
1. Effect of pH on vascular smooth muscle contraction was analyzed by use of biochemical and pharmacological techniques. 2. In the aorta isolated from spontaneously hypertensive rats (SHR) decreasing extracellular pH (pH0) caused a rapid acidification of intracellular pH accompanied by a pH0-dependent increase in tension. The contraction of the SHR aorta was remarkable compared with that of the Wistar Kyoto rat (WKY) aorta. 3. Removal of NH4Cl caused a transient decrease in intracellular pH followed by a marked increase in tension. 4. Both contraction and intracellular Ca2+ mobilization induced by acidic pH0 were markedly inhibited by removal of extracellular Ca2+, verapamil and adenosine, whereas these were not affected by tetrodotoxin or Gd3+, a stretch-activated cation channel blocker. Furthermore, cromakalim (a K+ channel opener) inhibited acidic pH0-induced contraction (APIC). 5. Acidic pH0 induced a depolarization of cultured smooth muscle cells from SHR aorta. 6. Blood pressure elevated with increasing age of WKY and SHR accompanied by an increase in APIC. Feeding WKY with NG-nitro-L-arginine, an inhibitor of nitric oxide synthases caused a marked elevation of their blood pressure followed by an increase in APIC. 7. These results suggest that APIC is caused by Ca2+ influx mediated through the activation of voltage-sensitive Ca2+ channels mainly due to acidic pH0-induced depolarization of the plasma membrane of smooth muscle cells. It is also suggested that APIC is strengthened by the elevation of blood pressure.
Furukawa
K
K
Department of Pharmaceutical Molecular Biology, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
Komaba
J
J
Sakai
H
H
Ohizumi
Y
Y
D000143:Acids / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D006224:Cricetinae; D006863:Hydrogen-Ion Concentration; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects*; D011189:Potassium Chloride / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013997:Time Factors
D000143:Acids; D011189:Potassium Chloride