Intracerebroventricular metformin attenuates salt-induced hypertension in spontaneously hypertensive rats.

Abstract The aim of this study was to examine the effects of long-term continuous intracerebroventricular (icv) infusion of metformin on blood pressure (BP) in spontaneously hypertensive rats (SHR). To accelerate the development of hypertension, SHR were fed a 8% NaCl diet during the 3-week study period. Metformin was given in the following doses: 0 (isotonic saline; n = 7), 25 ( n = 8), 50 ( n = 6), 100 ( n = 6), and 200 μg/day icv ( n = 5). Mean arterial pressure (MAP) and heart rate (HR) were measured by radiotelemetry, and as a measure of the contribution of sympathetic nerve activity to BP, the decrease in MAP in response to ganglionic blockade with hexamethonium, 30 mg/kg iv, was determined once weekly. In vehicle treated rats, MAP increased by 27 ± 4 mm Hg, whereas in rats treated with a low dose of metformin (25 μg/day), MAP increased only by 7 ± 3 mm Hg ( P