Protein kinase C activation selectively augments a stretch-induced, calcium-dependent tone in vascular smooth muscle

Abstract

The interaction of the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) with vascular tone due to histamine, high K+ and stretch were studied in the rabbit facial vein. Segments were incubated in physiological salt solution (PSS) containing Ca++ (1.6 mM) and an optimal preload was applied. Myogenic or stretch-induced tone was studied in two ways. Vessels were stretched in PSS at 28 degrees C and the bath temperature was gradually increased in a standard manner. Alternatively, vessels stretched at 42 degrees C were placed in zero-Ca++ PSS at the same temperature and responses to readmission of Ca++ to the PSS recorded. TPA (0.01 or 0.1 microM for 1 hr), a protein kinase C activator, consistently enhanced myogenic responses to stretch initiated by either procedure. It had very little effect or even depressed the tone due to histamine of high K+. The selective effect of protein kinase C activation on stretch-induced, Ca++-dependent myogenic tone argues for a pathway in this vessel activated selectively by stretch that may be modulated by protein kinase C-dependent mechanisms. It is proposed that stretch of the rabbit facial vein opens specific Ca++ entry pathways; the interaction of TPA with those pathways may be such that TPA increases Ca++ sensitivity or availability.