THE MECHANISM OF ACIDIC PH-INDUCED CONTRACTION IN AORTAE FROM SHR ANDWKY RATS ENHANCED BY INCREASING BLOOD-PRESSURE

1 Effect of pH on vascular smooth muscle contraction was analyzed by u se of biochemical and pharmacological techniques. 2 In the aorta isola ted from spontaneously hypertensive rats (SHR) decreasing extracellula r pH (pH,) caused a rapid acidification of intracellular pH accompanie d by a pH(o)-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 intracellula r pH followed by a marked increase in tension. 4 Both contraction and intracellular Ca2+ mobilization induced by acidic pH, were markedly in hibited by removal of extracellular Ca2+, verapamil and adenosine, whe reas these were not affected by tetrodotoxin or Gd3+, a stretch-activa ted cation channel blocker. Furthermore, cromakalim (a K+ channel open er) inhibited acidic pH(o)-induced contraction (APIC). 5 Acidic pH(o) induced a depolarization of cultured smooth muscle cells from SHR aort a. 6 Blood pressure elevated with increasing age of WKY and SHR accomp anied by an increase in APIC. Feeding WKY with NG-nitro-L-arginine, an inhibitor of nitric oxide synthases caused a marked elevation of thei r blood pressure followed by an increase in APIC. 7 These results sugg est that APIC is caused by Ca2+ influx mediated through the activation of voltage-sensitive Ca2+ channels mainly due to acidic pH(o)-induced depolarization of the plasma membrane of smooth muscle cells. It is a lso suggested that APIC is strengthened by the elevation of blood pres sure.