ISCHEMIA-INDUCED PERIPHERAL ARTERIAL VASOSPASM ROLE OF ALPHA(1)-ADRENOCEPTORS AND ALPHA(2)-ADRENOCEPTORS

Ischemia produces functional and structural alterations in peripheral blood vessels, Our study was designed to investigate alpha-adrenocepto r modifications induced by prolonged ischemia and their role in enhanc ing the contractile response during reperfusion in canine femoral arte ries. Unilateral vessel ischemia was created by double crossclamping a femoral artery and was maintained for 3 hr, Reperfusion was allowed f or 1 hr, The contralateral femoral artery was utilized as a control. T he vessels were harvested for contractile and binding studies. Isometr ic tension studies revealed that the magnitude of the maximum contract ile response to norepinephrine (NE), potassium chloride (KCl), and met hoxamine was 671 +/- 82 mg/mm(2) versus 245 +/- 43 mg/mm(2) (P < 0.01) , 485 +/- 46 mg/mm(2) versus 229 +/- 62 mg/mm(2) (P < 0.05), and 486 /- 88 mg/mm(2) versus 126 +/- 38 mg/mm(2) (P < 0.01), respectively for ischemic and nonischemic femoral arteries, EC(50) values showed that ischemic vessels were more sensitive to NE, KCl, and methoxamine (P < 0.05), Sodium nitroprusside induced concentration-dependent and comple te relaxation in all arterial rings (100% relaxation) but the ischemic femoral artery showed less sensitivity (P < 0.05). Binding studies sh owed that the number of binding sites (B-max) for [H-3]Prazosin and [H -3]Rauwolscine were significantly increased in ischemic versus nonisch emic vessels (1261 +/- 95 fmole/mg versus 704 +/- 113 fmole/mg, P < 0. 03, and 490 +/- 86 fmole/mg versus 175 +/- 15 fmole/mg, P < 0.04, resp ectively). Furthermore, a significant decrease in affinity (K-d) for [ H-3]Prazosin and [H-3]Rauwolscine was observed in ischemic versus noni schemic tissues (9.4 +/- 1.7 nM versus 4 +/- 0.2 nM, P < 0.02, and 6.4 +/- 1.5 nM versus 1.8 +/- 0.6 nM, P < 0.01, respectively), The increa se in canine femoral artery vasoreactivity, following prolonged ischem ia, seems to be also due to an increased density and functional activi ty of alpha-adrenoceptors expressed by the ischemic arterial smooth mu scle cells. (C) 1996 Academic Press, Inc.