Hemodynamic and sympathetic effects of fenoldopam and sodium nitroprusside.

Background: Fenoldopam is a novel dopamine-1 receptor selective agonist that can be used as a vasodilator perioperatively to treat hypertension and to produce induced hypotension. We were interested to find out whether there were any differences between fenoldopam (FM) and sodium nitroprusside (SNP), one of the most popular vasodilators, in their effects on hemodynamics and sympathetic outflow using not only neuraxis intact but also baro-denervated animal models.

Methods: A total of 60 New Zealand white rabbits were divided into two groups of 30 each: the neuraxis-intact group and the totally baro-denervated group. Each group was further divided into three groups of 10 each to receive SNP 10 microg x kg(-1), FM 10 microg x kg(-1) or FM 20 microg x kg(-1), respectively. Mean arterial pressure (MAP), heart rate (HR) and renal sympathetic nerve activity (RSNA) were recorded before and after intravenous (i.v.) administration of each agent. In addition, cardiac and sympathetic baroreflex sensitivity were assessed in the neuraxis-intact animals.

Results: In the neuraxis-intact groups, although RSNA was increased to a similar extent in all three groups (P<0.01), the reduction of MAP with FM groups was significantly greater than with SNP (P<0.05). HR was increased only in the SNP group. Cardiac (HR) and sympathetic barosensitivity were significantly attenuated with FM 20 microg x kg(-1) as compared to the SNP group. In the baro-denervated groups, there were significant and similar degrees of reduction of MAP in all three group up to 1 min (P<0.01). MAP remained significantly decreased in the FM groups for 10 min (only 2 min with SNP) in both animal models.

Conclusions: Unlike sodium nitroprusside, fenoldopam attenuates both cardiac (heart rate) and sympathetic baroreflex sensitivity, which may explain the lack of rebound hypertension with fenoldopam. The offset of hypotensive effects of fenoldopam is a significantly slower process as compared to nitroprusside, and this may be an unfavorable feature of fenoldopam should overshoot of hypotension occur.