Preferential renal and mesenteric vasodilation induced by barnidipine and amlodipine in spontaneously hypertensive rats

Barnidipine is a stereoselective, single isomer formulation of a long-term acting dihydropyridine calcium antagonist (CaA). In anaesthetised animals, the antihypertensive response to barnidipine is accompanied by a diuretic e ffect. The aim of the present study was to examine whether barnidipine incr eased renal blood flow in a conscious animal model for essential hypertensi on. We compared the regional specific hemodynamic effects of barnidipine wi th those obtained with its racemic mixture and amlodipine. Male adult spont aneously hypertensive rats (SHR) were instrumented with Doppler flow probes and catheters to measure renal (RVR), mesenteric (MVR) and hindquarter (HQ VR) vascular resistance changes. One week after surgery, barnidipine, its r acemic mixture, and amlodipine were intravenously administered at three dos es (n greater than or equal to 10 per dose) causing comparable reductions i n mean arterial pressure (MAP). At doses of 3, 10 and 30 mug/kg barnidipine reduced MAP (SEM), by 8 +/-2, 26 +/-3 and 45 +/-4 mmHg. Equipotent effects on MAP were achieved by the racemic mixture of barnidipine at 10, 30 and 1 00 mug/kg, and by amlodipine at doses of 100, 300 and 1000 mug/kg. Followin g the 3 mug/kg and 10 mug/kg dose, barnidipine reduced MVR (% +/- SEM) by 4 +/-4 and 19 +/-4, and RVR by 8 +/-2 and 15 +/-4, respectively. In contrast , HQVR remained unaltered. Similar data were obtained for the racemic mixtu m of barnidipine and for amlodipine, although for the latter the changes in RVR were half of those found after barnidipine. After the highest doses of barnidipine, its racemic mixture as well as amlodipine, HQVR, fell more th an 25% whereas RVR and MVR remained unaltered. Analysis of the dynamic resp onse to the CaAs revealed that the reductions in vascular resistance were a ssociated with decreased myogenic-like oscillations in blood flow. We concl ude that, in conscious SHR, the single isomer barnidipine reduces MAP at do ses which are three times lower than its racemic mixture and 30 times lower than amlodipine. In contrast to short-acting CaAs such as nifedipine and i sradipine, which reduce mainly HQVR and do not reduce RVR (Nievelstein et a l.; Eur J Pharmacol 113:187-198, 1985), the three long-term acting CaAs pre ferentially dilated the mesenteric and renal vascular bed. In view of the e levation of RVR in essential hypertension, the reduction of RVR may contrib ute to the long-term antihypertensive effects of barnidipine and amlodipine .