Effects of cGMP on Coordination of Vascular Smooth Muscle Cells of Rat Mesenteric Small Arteries

Abstract

Objective: We tested the hypothesis that cGMP can induce a state of only partial coordination of vascular smooth muscle cells (VSMC). Methods: This was done by studying the concentration-dependent effect of 8Br-cGMP on isometric and isobaric force development of noradrenaline-activated segments of rat mesenteric small arteries in which the endothelium was removed. We further measured the concentration-dependent effect of 8Br-cGMP on VSMC membrane potential, spatially resolved [Ca²⁺]_i and VSMC membrane conductance. Results: With 300 µ M 8Br-cGMP, coordinated [Ca²⁺]_i activity and vasomotion were seen as previously reported. At 10–30 µ M 8Br-cGMP, beating isometric tension oscillations were seen. Isobaric recordings revealed oscillations with different frequencies in different parts of the arteries. At these (10–30 µ M) 8Br-cGMP concentrations, membrane potential oscillations did not always concur with isometric tension oscillations, and [Ca²⁺]_i oscillations were only synchronized locally within groups of cells. 8Br-cGMP concentration-dependently decreased the frequency of vasomotion and, in unsynchronized hyperpolarized VSMC, the frequency of [Ca²⁺]_i waves. Conclusion: Our results demonstrated that cGMP can cause a partial coordination of the VSMC in the vascular wall (and at high concentrations near complete coordination). Furthermore, the cGMP concentration-dependent decrease of Ca²⁺ wave frequency and of vasomotion frequency suggests that cGMP modifies oscillatory Ca²⁺ release from the sarcoplasmic reticulum and supports the suggestion that this oscillatory release paces vasomotion.