Divergence of ANF analogs in smooth muscle cell cGMP response and aorta vasorelaxation: Evidence for receptor subtypes

Summary ANF analog potencies in stimulating smooth muscle cell cGMP were compared with the ability to relax histamine-constricted rabbit aorta in vitro . ANF[1–28] 3 , [5–28], [5–27] and Lys-11[5–28] elevated cGMP and were potent vasorelaxants. ANF[7–23] and Lys-11[7–23] were potent cGMP stimulators but 1000-fold weaker relaxants. Tyr-8[5–27] did not stimulate cGMP synthesis or antagonize the response of the other peptides, yet was a potent vasorelaxant. Crosslinking with 125 I-ANF identified bands at 150 and 65 KD by SDS-PAGE. ANF[1–28], Lys-11[7–23] and Tyr-8[5–27] blocked crosslinking at low-concentration despite disparate activities. These data support the existence of ANF receptor subtypes and suggest that cGMP elevation alone is not sufficient to promote atrial peptide-induced vasorelaxation.