Mechanisms of Enhanced Pressor Responses in Early Stage of One-Kidney, One Clip Hypertension in Rats

Pressor responses to vasoconstrictors are increased in both clinical and experimental hypertension. Previous studies from our laboratory showed exaggerated pressor responses to vasoconstrictors in prehypertensive rabbits of renal hypertension. Although these results have revealed important roles of several humoral factors such as renin-angiotensin system and prostaglandin systems, many other humoral factors and neurological mechanisms may be involved in enhanced pressor responses. Furthermore, humoral factors could modulate vascular reactivity via neurogenic system, e.g. baroreflex. The present study examined 1) a role of angiotensin II in enhanced pressor responses in early stage of one-kidney, one clip renal hypertension in rats (2 days after renal artery stenosis : 2-day clipped rats), using [1-Sar, 8-Ile] angiotensin II, specific antagonist of angiotensin II ; 2) a role of serotonin, one of the other humoral factors, in the enhanced pressor responses in this model, using ketanserin, a specific antagonist of 5-HT2 ; and 3) changes in baroreflex sensitivity to determine whether baroreflex causally relates to this pressor hyperresponsiveness. Mean arterial pressure was slightly higher in the 2-day clipped rats than in sham-operated rats. Pressor responses to norepinephrine, arginin vasopressin and serotonin were exaggerated in the 2-day clipped rats than in the sham-operated rats. This hyperresponsiveness was attenuated by administering [1 -Sar, 8 -Ile] angiotensin II and ketanserin either of which did not alter mean arterial pressure. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in responses to bolus injections of phenylephrine. Baroref ex sensitivity was not decreased but markedly increased in the 2-day clipped rats and was unaffected by the infusion of [1-Sar, 8-Il] angiotensin II. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to norepinephrine, arginin vasopressin and serotonin ; 2) angiotensin II and serotonin play significant roles in these increased pressor responses ; and 3) the changes in baroreflex sensitivity do not participate in the pressor hyperresponsiveness in the 2-day clipped rats, because the increased sensitivity should have attenuated this response, not exaggerated it.