Effect of tienilic acid on the electromechanical properties of vascular smooth muscles in normotensive and spontaneously hypertensive rats.

The membrane potential and ionic currents of smooth muscle strips of the portal vein were studied in normotensive rats (WKY) and spontaneously hypertensive rats (SHR) by the double sucrose gap. The parameters of the membrane, i.e., resting potential, action potential, and maximal amplitudes of Ca and K currents were similar in WKY and SHR preparations. The maximal rate of rise of isometric contractions was increased in SHR as compared to WKY rats. The smooth muscle membrane of SHR rats was also more sensitive to noradrenaline, i.e., depolarization of the membrane appeared with 5 X 10(-9) M noradrenaline in SHR, but with 5 X 10(-8) M in WKY rats. Depolarization block of all-or-nothing action potential generation appeared at a lower concentration of noradrenaline in SHR preparations. Sensitivity of the smooth muscle membrane to angiotensin II and prostaglandin E1 was also higher in SHR as compared to WKY rats. Tienilic acid (TA, 5 X 10(-5) M) depressed both action potential and contraction amplitudes in both WKY and SHR preparations. The inward Ca current was reduced, but the K current was not. Chronic administration of TA to SHR (6 months) suppressed the increased sensitivity to noradrenaline, angiotensin II, and prostaglandin E1. The results suggest that TA acts primarily on the plasma surface of vascular smooth muscle by reducing the inward Ca current, and may, in this way, decrease both cytoplasmic Ca concentration and vascular contractility in SHR.