C-NATRIURETIC PEPTIDE BUT NOT ATRIAL-NATRIURETIC-PEPTIDE INCREASES CYCLIC-GMP IN CEREBRAL ARTERIAL SMOOTH-MUSCLE CELLS

A-type natriuretic peptide (ANP) is found primarily in the heart and i s released into the circulation. C-type (CNP) is found principally in the brain and has also been detected in the systemic circulation. When injected, both peptides produce vasodilatation most likely by elevati on of guanosine 3'5'- cyclic monophosphate (cGMP) in smooth muscle cel ls via two distinct receptors, NPR-A and NPR-B. In this present study, we determined the effects of these two peptides on intracellular cGMP in smooth muscle cells cultured from pig cerebral and peripheral arte ries. In smooth muscle cells cultured from the left anterior descendin g coronary artery, ANP and CNP increased cGMP with equal potency and e fficacy (EC(50) for ANP and CNP, 3.6 +/- 0.2 x 10(-8) M and 6.7 +/- 0. 8 x 10(-8) M, respectively). In contrast, in smooth muscle cells from cerebral arteries, ANP was without effect while CNP increased cGMP in a concentration dependent manner (EC(50): 9.6 +/- 1.7 x 10(-8) M). Sti mulation of the soluble guanylyl cyclase with either nitroglycerin or nitroprusside was equivalent in the two cell types. The pattern of res ponse of intracellular cGMP to CNP and ANP in isolated intact arteries from brain and heart was similar to that found in the cultured cells. These results suggest that smooth muscle cells in cerebral arteries e xpress only NPR-B while cells from peripheral arteries can express bot h NPR-A and NPR-B.