[Modulation of coronary vessel tonus: molecular and cellular mechanisms]

Abstract

The cyclic interactions between myosin cross bridges and the actin filament in the presence of Ca++ with a sliding of both filaments passed each other, is considered also in vascular smooth muscle as the basic contractile mechanism. While in the striated muscle the regulation of the actin-myosin interaction occurs at the level of the actin filaments, there is a growing body of evidence that the contractile activation of the vascular smooth muscle is primarily regulated by phosphorylation of the 20,000-Dalton myosin light chain. This reaction is catalyzed by a calcium-calmodulin-dependent myosin light chain kinase. Additionally, dephosphorylated myosin cross bridges which remain attached to actin filaments over prolonged periods of time ("latch bridges") at low myoplasmic Ca2+-concentrations seem to be involved in the vascular smooth muscle in maintaining tonic active stress at a very low energy expenditure. In most arterial smooth muscle cells, the initiation of contraction (electromechanical coupling) is not associated with action potentials, but is coupled with graded membrane depolarization. During the process of excitation-contraction coupling, two mechanisms lead to increased myoplasmic calcium: a) Calcium influx through voltage-dependent channels along an electro-chemical gradient. b) Release of calcium from the sarcoplasmic reticulum or from the inside of the cell membrane, triggered either by calcium influx or directly by membrane depolarization. The pharmaco-mechanical coupling, i.e., the contractile activation by drugs without depolarization as initiating step, seems to be realized only in a few specific vessels. The stimulation of the phosphatidyl-inositol turnover (PI-cycle) in the plasma membrane by activation of alpha 1-adrenergic receptors can also be demonstrated in vascular smooth muscle cells. However, whether or not this PI-response plays a primary role in the increase of myoplasmic Ca2+ remains to be settled. The activation of alpha 2-adrenergic receptors seems to involve the action of an inhibitory guanine nucleotide-binding protein on the catalytic moiety of the adenylate cyclase. Thus, the contractile response observed may be attributed to the decrease of cyclic AMP (which is responsible for dilating effects via phosphorylation of various regulatory proteins). The decrease in the myoplasmic concentration of free-ionized calcium as a basic principle of relaxation comes about by different mechanisms, which can be classified as follows: a) Inhibition of transmembrane calcium influx into vascular smooth muscle cells by Ca-antagonists, which specifically interfere with plasmalemmal Ca2+-channels.(ABSTRACT TRUNCATED AT 400 WORDS)