These studies evaluate the effects of atrial natriuretic peptide (ANP) and nitroprusside (NP) on cultured mesangial cells (MC) grown on a flexible silicone rubber surface. The basal tone of the MC produced wrinkles on the silicone rubber surface. A decrease in number or magnitude of wrinkles was considered to represent cell relaxation, whereas an increase represented cell contraction. ANP (10(-9) M) produced a relaxation in greater than 60% of the cells by 10 min. The percentage of cells showing a decrease of wrinkles was significantly higher (P less than 0.05 at 5 min and P less than 0.001 at 10 min) during the ANP-treated period than during the control period. NP (10(-5) M) caused a decrease of wrinkles in greater than 80% of cells (P less than 0.02 at 5 min and P less than 0.01 at 10 min) compared with a 5% decrease in the control period. Dibutyryl guanosine 3',5'-cyclic monophosphate (DBcGMP; 10(-4) M) also produced a decrease of wrinkles in 81% of the cells (P less than 0.02) compared with a 9% decrease in the control period. MC treated with ANP, NP, or DBcGMP and then labeled with 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD)-phallacidin did not show obvious alteration of morphology of actin filaments compared with untreated cells. ANP could inhibit as well as partially reverse the agonist (angiotensin II)-induced contractile response. ANP (10(-10)-10(-8) M) as well as NP (10(-5) M) increased intracellular cGMP content of MC (P less than 0.005) compared with control cells.(ABSTRACT TRUNCATED AT 250 WORDS)