In experimental models and in humans, somatostatin (SRIF) is able to contract certain vascular structures. The present experiments were designed to assess the capacity of SRIF to contract cultured rat aortic vascular smooth muscle cells (VSMC), and to analyze the possible mechanisms involved. Cells incubated with SRIF showed a significant reduction in planar cell surface area, in a time- and dose-dependent manner. This effect was partially blocked 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 phosphorylation in VSMC. A small but significant increase of intracellular calcium concentration, and decreased levels of cAMP, without changes in cGMP, were detected in VSMC incubated with SRIF. A search for the known SRIF receptors present in these cells, by reverse transcription-polymerase chain reaction, only SRIF receptor-4 was found to be present. These results demonstrate the ability of SRIF to contract cultured rat VSMC. The contraction observed 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 receptor-4. (C) 1999 Elsevier Science Inc. All rights reserved.