Maturational differences in soluble guanylate cyclase activity in ovine carotid and cerebral arteries

Abstract

Basal cGMP concentrations are greater in immature than in mature cranial arteries, which may help explain why cerebrovascular resistance is lower in neonates than in adults. The present studies explore the hypothesis that this difference derives from age-related differences in soluble guanylate cyclase (sGC) activity. Maturation depressed (p < 0.0l) maximal sGC activity (pmol cGMP/mg/min) in both carotid (from 11.10 ± 0.50 to 3.60 ± 0.20) and cerebral (from 3.10 ± 0.31 to 1.45 ± 0.08) arteries. Western blot analysis of relative sGC abundance (relative to sGC expression in adult kidney) found that sGC abundance was significantly greater (p < 0.05) in newborn carotid (0.38 ± 0.04) and cerebral arteries (0.37 ± 0.06) than in adult arteries (0.25 ± 0.05 and 0.17 ± 0.03, respectively). Basal K(m) values in carotid and cerebral arteries did not differ significantly between newborns (3- to 7- d old) and adults. Activation of sGC with nitrosylated heme significantly reduced K(m) values 3- to 5-fold in both types of artery and in both age groups. Within artery type, maturation had no significant effect on activated K(m). Between artery types, activated K(m) values were greater (p < 0.05) in cerebral (200 ± 40 μM) than in carotid (80 ± 10 μM) arteries. Together, these data suggest that variations in sGC substrate affinity contribute to observed differences in sGC activity between artery types but not those between age groups. In contrast, variations in enzyme abundance, and possibly also enzyme-specific activity, appear responsible for differences in sGC activity associated with both age and artery type.