Dilatation by angiotensin II of the rat femoral arterial bed in vivo via pressure/flow-induced release of nitric oxide and prostaglandins.

Abstract

1. The haemodynamic effects of angiotensin II (AII) and, for comparison, arginine vasopressin (AVP) in the femoral and superior mesenteric artery of urethane-anaesthetized rats were analysed with the ultrasonic transit time shift technique. 2. I.v. bolus injection of AII (0.1-3 nmol kg-1) and AVP (0.03-1 nmol kg-1) increased blood pressure which was accompanied by a decrease in blood flow through the superior mesenteric artery and an increase in femoral blood flow. The femoral hyperaemia was in part due to vasodilatation as indicated by a rise of femoral vascular conductance up to 200% relative to baseline. The femoral vasodilatation caused by AVP, but not AII, was followed by vasoconstriction. 3. Blockade of angiotensin AT1 receptors by telmisartan (0.2-20 mumol kg-1) prevented all haemodynamic responses to AII. 4. The femoral dilator responses to AII and AVP depended on the increase in vascular perfusion pressure since vasodilatation was reversed to vasoconstriction when blood pressure was maintained constant by means of a gravity reservoir. However, the AII-evoked femoral vasodilatation was not due to an autonomic or neuroendocrine reflex because it was not depressed by hexamethonium (75 mumol kg-1), prazosin (0.25 mumol kg-1) or propranolol (3 mumol kg-1). 5. The AII-induced femoral vasodilatation was suppressed by blockade of nitric oxide (NO) synthesis with NG-nitro-L-arginine methyl ester (L-NAME, 40 mumol kg-1) and reversed to vasoconstriction when L-NAME was combined with indomethacin (30 mumol kg-1), but was left unaltered by antagonism of endothelin ETA/B receptors with bosentan (37 mumol kg-1). 6. These results demonstrate that the effect of AII to increase systemic blood pressure and the resulting rise of perfusion pressure in the femoral artery stimulates the formation of NO and prostaglandins and thereby dilates the femoral arterial bed. This local vasodilator mechanism is sufficient to mask the direct vasoconstrictor response to AII.