Effects of brimonidine ingestion on cardiovascular responses and renal function in conscious dogs

The effects of brimonidine, an alpha(2)-adrenoceptor agonist, on blood pressure, heart rate, respiratory rate, renal function and some blood parameters were investigated in 10 dogs. Dogs were divided into two groups, low dose (LD; 0.2 mg/kg) and high dose (HD; 0.5 mg/kg) of brimonidine given orally. The alpha(2)-adrenergic antagonist yohimbine hydrochloride was injected to dogs at a dose of 0.1 mg/kg in both groups at the fifth hour after brimonidine administration. The results demonstrated that after administration of brimonidine, mean arterial blood pressure decreased dramatically at 2 h by 23% and 20% in LD and HD groups, respectively. Heart rate was decreased in a similar manner and both remained low at 5 h after brimonidine administration. Respiratory rate was decreased by 50%, while the electrocardiogram showed prolongation of the PR interval. Glomerular filtration rate (GFR) and effective renal blood flow were reduced when measured at 4 h after brimonidine ingestion in both groups, but the effect was more pronounced in the LD group. Brimonidine caused natriuresis and kaliuresis in both LD and HD groups. The packed cell volume was decreased and hyperglycaemia was detected. Most of the effects can be reversed completely after administration of yohimbine. However, yohimbine can restore GFR only partially. These data suggest that brimonidine caused cardiovascular and respiratory depression. The adverse effects of this drug can be antagonized by yohimbine, suggesting that these effects were mediated via the alpha(2)-adrenoceptor.