Endogenous cardiac vasoactive factors modulate endothelin production by cardiac fibroblasts in culture.

Endothelin, a potent vasoconstrictor, is produced by cardiac fibroblasts in culture and induces hypertrophy in cardiac myoctes. The purpose of this study was to determine whether vasoactive factors endogenous to the heart affect the production of endothelin by cultured cardiac fibroblasts. Vasoactive factors have been shown to play multiple roles in the adaptation of the heart to chronic overload, affecting both vascular tone and cell growth. Both atrial (ANP) and brain (BNP) natriuretic peptides are endogenous cardiac vasodilators and are produced by cultured myocytes in response to stimulation with endothelin. Treatment of cardiac fibroblasts with these peptides decreased endothelin production. Nitroprusside, an activator of guanylyl cyclase, decreased endothelin production indicating the involvement of cGMP in the response. Carbaprostacyclin, a stable derivative of prostacyclin, another endogenous cardiac vasodilator, also decreased endothelin production by fibroblasts. The combination of BNP and carbaprostacyclin was additive in decreasing endothelin production. In contrast, PGF2α and angiotensin II, both endogenous cardiac vasoconstrictors, increased endothelin production and overcame the inhibition induced by BNP and carba-prostacyclin. In summary, endothelin production by cardiac fibroblasts was decreased by the endogenous cardiac vasodilators ANP, BNP, and prostacyclin and increased by the endogenous vasoconstrictors PGF2α and angiotensin II.