This investigation was conducted to test whether topical nitroprusside (NP), a cytosolic guanylate cyclase activator, would increase the level of cyclic GMP and alter O-2 consumption or blood flow in the cerebral cortex of rats. Male Long-Evans rats were used in a control(n = 9), low dose NP (n = 13, 10(-3) M) or high dose NP (n = 12, 10(-2) M) group. Nitroprusside or saline was topically applied to the right side of the cerebral cortex and the left side was used as a control. The cyclic GMP level was determined in five rats in each group using a radioimmunoassay. In the other rats in each group, regional cerebral blood flow was measured by [C-14]iodoantipyrine and regional arterial and venous O-2 saturations were determined microspectrophotometrically. Nitroprusside significantly increased the cyclic GMP level from 21.4 +/- 12.0 pmol/g (contralateral cortex) to 52.2 +/- 36.7 pmol/g (NP treated cortex) in low dose nitroprusside group and from 19.9 +/- 22.6 pmol/g (contralateral cortex) to 58.5 +/- 15.1 pmol/g (NP treated cortex) in high dose nitroprusside group. High dose nitroprusside significantly increased cerebral blood flow from 80 +/- 11 ml.min(-1).100 g (contralateral cortex) to 114 +/- 11 ml.min(-1).100 g (NP treated cortex). However, there was no significant difference in O-2 extraction and O-2 consumption between the NP treated cortex and contralateral cortex in either the low or the high dose NP groups. In the high dose NP group, the O-2 extraction was 8.0 +/- 1.3 ml O-2.100 ml(-1) in the treated cortex and 8.8 +/- 1.5 ml O-2.100 ml(-1) in the contralateral cortex, while the O-2 consumptions in the NP treated cortex and contralateral cortex were 8.1 +/- 1.3 ml O-2.min(-1).100 g(-1) and 7.3 +/- 1.2, respectively. Thus, NP increased the cyclic GMP level without a significant change in O-2 consumption in the cerebral cortex. Our data suggested that O-2 consumption in the cerebral cortex was not affected by the increased level of cyclic GMP.