ObjectivesVascular beds vary in their responses to atrial natriuretic peptide and sodium nitroprusside. Both of these agents dilate blood vessels by increasing intracellular guanosine 3',5'-cyclic monophosphate (cyclic-GMP) but activate different enzymes in the vascular smooth muscle cell. We aimed to determine if the response of intracellular cyclic-GMP to atrial natriuretic peptide and sodium nitroprusside varies in smooth muscle cells cultured from different vascular beds.DesignProspective, repeated measures analysis of concentration-response curves.SettingAnesthesia research laboratory of an academic medical center.SubjectsGuinea pigs: Cultured guinea pig smooth muscle cells were obtained from three different blood vessels.InterventionsNone.Measurements and Main ResultsIntracellular cyclic-GMP was measured by radioimmunoassay and concentration-response curves of cyclic-GMP to atrial natriuretic peptide and sodium nitroprusside were determined.Cells from the thoracic aorta were the most responsive to atrial natriuretic peptide. Atrial natriuretic peptide (1 μM) increased cyclic-GMP concentrations to 72 ± 5 pmol/mg (20-fold increase) with a 50% effective concentration of 3 nM. The concentration-response curve in epicardial coronary smooth muscle cells was to the right with an 50% effective concentration for atrial natriuretic peptide of 20 nM and a maximum response of a ten-fold increase in cyclic-GMP. Coronary resistance vessel cells were unresponsive to atrial natriuretic peptide. In response to sodium nitroprusside, the concentration-response curve in coronary resistance vessel cells was significantly to the left of either thoracic aorta cells or the epicardial coronary cells. The 50% effective concentration for sodium nitroprusside in coronary resistance vessel smooth muscle cells was ∼1 μM, while in both thoracic aortic cells and epicardial coronary cells, the 50% effective concentration was ten times higher. Coronary resistance cells were the most responsive with a 62-fold increase in cyclic-GMP in response to 1 mM of sodium nitroprusside. The maximum response in thoracic aorta cells and epicardial cells was 20− and 30-fold, respectively.ConclusionsSmooth muscle cells respond differently to vasodilators. The response of these cultured cells mimics the response of the intact vascular bed from which they were obtained. These findings suggest that phenotypic properties of smooth muscle cells within a blood vessel contribute to the responsiveness of the vessel. (Crit Care Med 1994; 22:1461–1464)