Antihypertensive and orthostatic responses to drugs in conscious dogs

In view of the frequent occurrence of orthostatic hypotension in antihypertensive therapy, the orthostatic potential of various classes of drugs was evaluated in conscious normotensive dogs in order to assess the utility of this model. Antihypertensive effectiveness was ascertained initially in hypertensive dogs. Inhibitors of peripheral sympathetic vasoconstrictor mechanism (phentolamine, prazosin, guanethidine) produced marked orthostatic hypotension at antihypertensive doses. In contrast, clonidine did not. The vasodilator hydralazine and, to some extent, minoxidil also caused postural effects. It is concluded that conscious dogs are useful in assessing the orthostatic potential of antihypertensive drugs but that their predictability to humans is not universal.