The mechanism of acidic pH‐induced contraction in aortae from SHR and WKY rats enhanced by increasing blood pressure

• Published in: British journal of pharmacology Vol. 118; no. 3; pp. 485 - 492
• Main Authors: Furukawa, Ken‐Ichi, Komaba, Junji, Sakai, Hiroyuki, Ohizumi, Yasushi
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.06.1996; Nature Publishing
• Subjects: acidosis; Acids - pharmacology; Animals; Aorta - drug effects; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; blood pressure; Blood Pressure - drug effects; Ca2+ mobilization; Cardiology. Vascular system; Cricetinae; Experimental diseases; fura‐2; Hydrogen-Ion Concentration; hypertension; K+ channel; Male; Medical sciences; Membrane Potentials - drug effects; Muscle Contraction - drug effects; NG‐nitro‐L‐arginine; Potassium Chloride - pharmacology; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spontaneously hypertensive rats; Time Factors; vascular smooth muscle; voltage‐sensitive Ca2+ channel; Hypertension; Pathophysiology; Rat; Rodentia; Cardiovascular disease; Smooth muscle; Hereditary; Muscle contraction; Thoracic aorta; Vertebrata; Mammalia; Animal; Blood vessel; pH
• ISSN: 0007-1188; 1476-5381
• DOI: 10.1111/j.1476-5381.1996.tb15429.x

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 (pHo) caused a rapid acidification of intracellular pH accompanied by a pHo‐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 pHo 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 pHo‐induced contraction (APIC). 5 Acidic pHo 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 pHo‐induced depolarization of the plasma membrane of smooth muscle cells. It is also suggested that APIC is strengthened by the elevation of blood pressure.