Vasodilatation induced by forskolin involves cyclic GMP production

Mário dos Anjos Neto, Claure Nain Lunardi, Gerson Jhonatan Rodrigues, Lusiane Maria Bendhack

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DOI: 10.4236/jbpc.2011.24042                

Abstract

Endothelium-derived relaxing factors contribute to smooth muscle relaxation. The aim of the present study was to investigate the contribution of nitric oxide (NO) produced in the endothelial cells to the vasodilatation stimulated with forskolin in rat aorta. Forskolin that directly activates adenylyl-cyclase, induced complete relaxation in phenylephrine-contracted aortas. Endothelium removal reduced the potency (pEC₅₀) of forskolin without changes in the maximum effect (Emax). However, the inhibitor of endothelial NO-synthase (10 μM L- NG-Nitroarginine, L-NNA) reduced both Emax and pEC₅₀ in intact endothelium aortic rings. L-NNA or L-NNA plus cyclooxygenase inhibitor indomethacin (10 μM) reduced both Emax and pEC₅₀ of forskolin. Forskolin increased both the cytosolic Ca⁺² concentration and the cytosolic NO concentration ([NO]c) in the endothelial cells. The PKA inhibitor KT5720 reduced the NO production activated by forskolin in the endothelial cells. The enhanced [NO]c in the endothelial cells increased cyclic guanosine-monophosphate (cGMP) in smooth muscle cells, which was abolished by L-NNA. Taken together, our results indicate that vasodilatation mediated by forskolin in rat aortic rings is potentiated by NO production in endothelial cells that increases the cGMP levels in the smooth muscle cells that along with cAMP contribute to the vasodilatation.

Keywords

Forskolin; Cytosolic Calcium; cAMP; cGMP; Endothelial Cells; Nitric Oxide

Conflicts of Interest

The authors declare no conflicts of interest.

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