Relaxation of retinal pericyte contractile tone through the nitric oxide-cyclic guanosine monophosphate pathway.

PURPOSE Pericytes are contractile cells outside the endothelial lining of capillaries. The study investigated whether nitric oxide, known to cause relaxation of vascular smooth muscle cells, also relaxes pericytes. METHODS Cultured bovine pericytes were exposed to a nitric oxide donor, sodium nitroprusside, and to 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo cGMP) in the presence and in the absence of methylene blue, an inhibitor of guanylate cyclase. Relaxation was assessed by counting the loss of wrinkles induced by pericytes when they are cultured on thin sheets of silicone. Intracellular cyclic guanosine monophosphate (cGMP) was measured by radioimmunoassay. RESULTS Pericytes relaxed to sodium nitroprusside (3 x 10(-8) to 10(-4) M) in a concentration-dependent manner (ED50: 10(-6) M). The maximal response was characterized by the loss of almost all the wrinkles. The half-maximal relaxation was strongly inhibited by methylene blue (3 x 10(-7) M). Sodium nitroprusside (3 x 10(-6) M) caused a 14-fold increase in the intracellular concentration of cGMP, an effect inhibited by methylene blue (3 x 10(-7) M). The cGMP analogue, 8-bromo-cGMP (10(-5) and 3 x 10(-5) M) strongly relaxed the cells in a concentration-dependent manner, but the relaxation was not reduced by methylene blue (3 x 10(-7) M). CONCLUSIONS Sodium nitroprusside, which releases nitric oxide, strongly relaxes pericytes through an increase of cGMP. Therefore, the presence of the endothelium-derived relaxing factor nitric oxide in the microcirculation can modulate the tone of pericytes, and it thus has the potential to influence blood flow in capillaries.