CHRONIC INFUSION OF LOW-DOSE ANGIOTENSIN-II POTENTIATES THE ADRENERGIC RESPONSE IN-VIVO

Objective The aim of this study was to investigate the role of angiote nsin II-induced potentiation of the alpha(1)-adrenergic contractile re sponse in the aetiology of low-dose angiotensin II-induced hypertensio n. Methods Wistar rats (250 g) received angiotensin II (120 ng/kg per min) from subcutaneous minipumps for 21 days. The responses of vase-ac tive properties of second-order mesenteric arteries (200 mu m) to pota ssium, phenylephrine, angiotensin II and acetylcholine were assessed. The acute amplification effects of angiotensin II on the response to p henylephrine were examined, Results Angiotensin II induced a progressi ve hypertension, which reached a plateau after approximately 5 days. T he responses to potassium, angiotensin II and acetylcholine were not s ignificantly modified in rats treated chronically with angiotensin II. The major finding of this study is that the response to phenylephrine (1-3 mu mol/l) was potentiated (sevenfold at 1.75 mu mol/l) after chr onic treatment with angiotensin II. In control vessels acute addition of angiotensin II (10(-10) mol/l) produced no contraction but induced potentiation of the phenylephrine response (1-3 mu mol/l). No further potentiation of the phenylephrine response was observed in the rats tr eated chronically with angiotensin II. Conclusions Thus, although the direct contractile responses to potassium and angiotensin II remain un affected following chronic angiotensin II treatment, the alpha(1)-adre nergic contractile response to phenylephrine is significantly potentia ted by angiotensin II in this model of hypertension. We suggest that t his potentiation contributes to the hypertension observed in response to infusion of low-dose angiotensin II.