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 [Ca(2+)](i) and VSMC membrane conductance.

Results: With 300 microM 8Br-cGMP, coordinated [Ca(2+)](i) activity and vasomotion were seen as previously reported. At 10-30 microM 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 microM) 8Br-cGMP concentrations, membrane potential oscillations did not always concur with isometric tension oscillations, and [Ca(2+)](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 [Ca(2+)](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 Ca(2+) wave frequency and of vasomotion frequency suggests that cGMP modifies oscillatory Ca(2+) release from the sarcoplasmic reticulum and supports the suggestion that this oscillatory release paces vasomotion.