Blood pressure reduction induced by chronic intracerebroventricular or peroral clonidine administration in rats with salt-dependent or angiotensin II-dependent hypertension

Abstract

The agonists of alpha(2)-adrenergic receptors such as clonidine, rilmenidine or monoxidine are known to lower blood pressure (BP) through a reduction of brain sympathetic outflow but their chronic antihypertensive effects in rats with low-renin or high-renin forms of experimental hypertension were not studied yet. Moreover, there is no comparison of mechanisms underlying BP reduction elicited by chronic peroral (po) or intracerebroventricular (icv) clonidine treatment. Male salt-sensitive Dahl rats fed 4% NaCl diet and Ren-2 transgenic rats were treated with clonidine administered either in the drinking fluid (0.5 mg/kg/day po) or as the infusion into lateral brain ventricle (0.1 mg/kg/day icv) for 4 weeks. Basal BP and the contributions of renin-angiotensin system (captopril 10 mg/kg iv) or sympathetic nervous system (pentolinium 5 mg/kg iv) to BP maintenance were determined in conscious cannulated rats at the end of the study. Both peroral and intracerebroventricular clonidine treatment lowered BP to the same extent in either rat model. However, in both models chronic clonidine treatment reduced sympathetic BP component only in rats treated intracerebroventricularly but not in perorally treated animals. In contrast, peroral clonidine treatment reduced angiotensin II-dependent vasoconstriction in Ren-2 transgenic rats, whereas it lowered residual blood pressure in Dahl rats. In conclusions, our results indicate different mechanisms of antihypertensive action of clonidine when administered centrally or systemically.

Fig. 1

Blood pressure effects of chronic peroral (po, 0.5 mg/kg/day) or intracerebroventricular (icv, 0.1 mg/kg/day) administration of clonidine to male salt-sensitive Dahl rats fed high-salt diet (4 % NaCl). MAP – basal mean arterial pressure, RAS blockade – MAP change after acute captopril injection (10 mg/kg iv), SNS blockade – MAP change after acute pentolinium injection (5 mg/kg iv), NOS blockade – MAP change after acute L-NAME injection (30 mg/kg iv). Data are means ± SEM, number of animals are given at the bottom of the columns. * significantly different (p<0.05) from the controls.

Fig. 2

Blood pressure effects of chronic peroral (po, 0.5 mg/kg/day) or intracerebroventricular (icv, 0.1 mg/kg/day) administration of clonidine to male heterozygous Ren-2 transgenic rats fed Altromin diet (0.45 % NaCl). MAP – basal mean arterial pressure, RAS blockade – MAP change after acute captopril injection (10 mg/kg iv), SNS blockade – MAP change after acute pentolinium injection (5 mg/kg iv), NOS blockade – MAP change after acute L-NAME injection (30 mg/kg iv). Data are means ± SEM, number of animals are given at the bottom of the columns. * significantly different (p<0.05) from the controls.