Role of ERK and Rho kinase pathways in central pressor action of urotensin II

Background: It has been shown that central urotensin II acts on the central nervous system to increase arterial pressure in conscious rats. Objective: To investigate the intracellular signal transduction mechanisms of the central cardiovascular action of urotensin II. Methods: The effects of intracerebroventricular (i.c.v.) administration of the extracellular signal-regulated protein kinase (ERK) inhibitor, PD 98059 (20 nmol), the phosphatidylinositol 3 (PI3) kinase inhibitor, wortmannin (20 nmol), or the Rho kinase inhibitor, Y-27632 (20 nmol), on cardiovascular responses to i.c.v. urotensin II (10 nmol) were determined in conscious rats. Results: I.c.v. injection of urotensin II increased both arterial pressure and heart rate (14.9 ± 1.5 mmHg and 94.6 ± 12.8 beats/min, respectively; P < 0.05 for each). Pretreatment with PD 98059 or Y-27632 significantly (P < 0.01 and P < 0.05, respectively) attenuated the pressor response induced by i.c.v. urotensin II (6.6 ± 1.4 and 6.9 ± 1.2 mmHg, respectively). Pretreatment with a mixed solution of PD 98059 and Y-27632 failed to cause further suppression of the urotensin II-induced pressor responses (4.5 ± 0.9 mmHg). In contrast, pretreatment with i.c.v. wortmannin failed to influence the pressor response induced by i.c.v. urotensin II (12.6 ± 1.3 mmHg). The tachycardiac response induced by i.c.v. urotensin II was not influenced by pretreatment with PD 98059, Y-27632 or wortmannin. Conclusions: These findings suggest that the ERK and Rho kinase pathways, but not the PI3 pathway, may be involved in the central pressor action of urotensin II in conscious rats.