Role of nitric oxide synthase inhibition in the acute hypertensive response to intracerebroventricular cadmium

In the rat, intracerebroventricular (i.c.v.) injection of cadmium, a pollutant with long biological half‐life, causes a sustained increase in blood pressure at doses that are ineffective by peripheral route. Since cadmium inhibits calcium‐calmodulin constitutive nitric oxide (NO) synthase in cytosolic preparations of rat brain, this mechanism may be responsible for the acute pressor action of this heavy metal. To test this possibility, we evaluated the effect of i.c.v. injection of 88 nmol cadmium in normotensive unanaesthetized Wistar rats, which were i.c.v. pre‐treated with: (1) saline (control), (2) L‐arginine (L‐Arg), to increase the availability of substrate for NO biosynthesis, (3) D‐arginine (D‐Arg), (4) 3‐[4‐morpholinyl]‐sydnonimine‐hydrochloride (SIN‐1), an NO donor, or (5) CaCl2, a cofactor of brain calcium‐calmodulin‐dependent cNOSI. In additional experiments, the levels of L‐citrulline (the stable equimolar product derived from enzymatic cleavage of L‐Arg by NO synthase) were determined in the brain of vehicle‐ or cadmium‐treated rats. The pressor response to cadmium reached its nadir at 5 min (43±4 mmHg) and lasted over 20 min in controls. L‐Citrulline/protein content was reduced from 35 up to 50% in the cerebral cortex, pons, hippocampus, striatus, hypothalamus (P