Tissue angiotensin II and endothelin-1 modulate differently the response to flow in mesenteric resistance arteries of normotensive and spontaneously hypertensive rats

1 In resistance arteries pressure-induced (myogenic) tone (MT) and flow (shear stress)-induced dilation (FD) are potent determinant of vascular resistance. We investigated the role of angiotensin II and endothelin-1 in FD and MT in resistance arteries and their potential change in hypertension. 2 Flow-diameter-pressure relationship was established in situ, under anaesthesia, in two daughter branches of a mesenteric resistance artery (180 mu M, n=7 per group) from spontaneously hypertensive (SHR) or normotensive (WKY) rats. One artery was ligated distally, so that it was submitted to pressure only, while the other was submitted to pressure and flow. Drugs were added to the preparation and external diameter, pressure and flow measured continuously. 3 External diameter (with flow) ranged from 150 +/- 3 to 191 +/- 7 mu M in WKY (n = 28) rats and from 168 +/- 6 to 186 +/- 6 mu M in SHR (n = 28). Flow induced a dilation of the non-ligated arteries which was lower in SHR (13 +/- 5 - 31 +/- 4 mu M vs WKY: 5 +/- 5 - 44 +/- 4 mu M). In the ligated artery, the diameter did not significantly change, due to MT. 4 In the vessels submitted to flow angiotensin converting enzyme inhibition (perindopril: 10 mu mol L-1) increased the diameter in SHR (+11 +/- 2 mu M) significantly more than in WRY (+2 +/- 1 mu M). Angiotensin type 1 receptor (AT(1)R) blockade (losartan, 10 mu mol L-1) increased the diameter in the vessels with flow in SHR only (+6 +/- 1 mu M). Angiotensin type 2 receptor (AT(2)R) blockade (PD 123319, 1 mu mol L-1) decreased arterial diameter in WKY only (9+/-2). Endothelin-1 type A receptor (ETAR) blockade (LU135252, 0.1 mu mol L-1) increased the diameter only in SHR in the artery submitted to flow (by 6 +/- 1 mu M). 5 Thus FD was counteracted by a flow-dependent AT(1) and ETA receptors-activation in SHR whereas in WKY FD AT(2)-dependent dilation is involved.