Mechanisms involved in the somatostatin-induced contraction of vascular smooth muscle cells

In experimental models and in humans, somatostatin (SRIF) is able to contra ct certain vascular structures. The present experiments were designed to as sess the capacity of SRIF to contract cultured rat aortic vascular smooth m uscle cells (VSMC), and to analyze the possible mechanisms involved. Cells incubated with SRIF showed a significant reduction in planar cell surface a rea, in a time- and dose-dependent manner. This effect was partially blocke d by preincubating the cells with a combination of calcium antagonists (10 mu M verapamil, plus 10 mu M 3,3,5-Trimrthoxybenzoic acid 3-(diethylanino) octyl ester TMB)-8). SRIF was also able to stimulate myosin light-chain pho sphorylation in VSMC. A small but significant increase of intracellular cal cium concentration, and decreased levels of cAMP, without changes in cGMP, were detected in VSMC incubated with SRIF. A search for the known SRIF rece ptors present in these cells, by reverse transcription-polymerase chain rea ction, only SRIF receptor-4 was found to be present. These results demonstr ate the ability of SRIF to contract cultured rat VSMC. The contraction obse rved in these cells appears to be due to a mixed mechanism, that involves [ Ca2+](i) and cAMP as second messengers, and is likely mediated via SRIF rec eptor-4. (C) 1999 Elsevier Science Inc. All rights reserved.