ELECTROMECHANICAL AND PHARMACOMECHANICAL COUPLING IN VASCULAR SMOOTH MUSCLE

Abstract

The electrical events accompanying contractions of helically cut vascular strips were studied by the sucrose gap method. Mechanical responses to drugs and caffeine were also determined in depolarized preparations. The isometric contractions of umbilical vein and pulmonary artery strips elicited by external electrical stimuli were observed. Norepinephrine, serotonin and histamine gradedly depolarized rabbit main pulmonary artery smooth muscle. There was some correlation between level of depolarization and drug concentrations. Drug-induced contractions were associated with lesser depolarization than the contractile response elicited by warming from room temperature to 35°C. Drugs or warming did not elicit repetitive action potentials in the rabbit main pulmonary artery preparations. Mesenteric vein strips of rabbits and dogs developed spontaneous action potentials associated with rhythmic contractions. Norepinephrine, serotonin, histamine and angiotensin produced depolarization and increased action potential frequency in these preparations. The absolute correlation between spike frequency and tension development was limited. Caffeine reversibly eliminated both the spontaneous and drug-induced action potentials of rabbit mesenteric veins without abolishing the resting membrane potential. The contractile response to drugs persisted, although it was diminished. The inequality of maximal mechanical responses to supramaximal concentrations of epinephrine, histamine and angiotensin was observed in preparations depolarized with potassium. The contractile response of electrically stimulated human umbilical veins was frequency-dependent. Graded, external electrical stimulation elicited graded contractions of rabbit main pulmonary artery strips. Caffeine had a diphasic mechanical effect on both polarized and depolarized vascular smooth muscle. We suggest the existence of two major electrophysiologic types of vascular smooth muscle, one gradedly responsive and the other producing repetitive action potentials. The mechanical response of the latter can be dissociated, with caffeine, from electrical spikes in the polarized state. Graded concentrations of drugs appear to elicit graded contractions through: 1) variable frequency spike electrogenesis; 2) graded depolarization; and 3) graded pharmacomechanical coupling. The inhibition-relaxation coupling mechanisms are also multiple and not solely dependent on inhibition of spike electrogenesis.