Absence of Reflex Sympathetic Activation by the Selective Renal Vasodilator CGP 22979A in the Conscious Rat

Abstract

The effects of the selective renal vasodilator prodrug CGP 22979A on mean arterial blood pressure (MAP), heart rate (HR) and sympathetic efferent splanchnic nerve activity (SpNA) were investigated in conscious normotensive rats, and compared with those of the active drug CGP 18137A, a hydrallazine-like systemic vasodilator. CGP 18137A (0.03 to lmg/kg i.v.) produced a dosedependent decrease in MAP, whereas HR and SpNA increased. CGP 22979A affected neither BP nor HR and SpNA at doses of 1 and 3mg/kg i.v. which induce a selective increase in renal blood flow. In contrast, a dose of 30mg/kg i.v., which produced systemic effects comparable to those of CGP 18137A, stimulated SpNA to the same extent as 18137A did. These results demonstrate that the rise in renal blood flow induced by low doses of CGP 22979A is not associated with an increase in efferent sympathetic nerve activity. They suggest also that selective renal vasodilatation can be accomplished without an activation of the sympathetic nervous system.

Key Words:

• renal vasodilatation
• sympathetic nerve activity
• prodrug