Effects of cGMP on coordination of vascular smooth muscle cells of rat mesenteric small arteries.
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.


CONCLUSIONS
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.
Rahman
Awahan
A
The Water and Salt Center, Institute of Physiology and Biophysics, University of Aarhus, Denmark.
Matchkov
Vladimir
V
Nilsson
Holger
H
Aalkjaer
Christian
C
D000818:Animals; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
C016276:8-bromocyclic GMP; D006152:Cyclic GMP; D002118:Calcium