Increased responsiveness of the vascular bed to angiotensin I, angiotensin II and phenylephrine in acute and chronic ischemic hindlimbs in rats.
Ischemia activates several compensatory mechanisms to restore blood supply. To investigate possible changes in the reactivity of blood vessels after acute and chronic ischemia of skeletal muscle, the response (resistance changes) of the vascular bed to angiotensin II (AII) and phenylephrine (PE) in a hindlimb perfusion model were studied in control, acutely ischemic (45 min) and chronically ischemic (4 weeks) spontaneously hypertensive rats. Furthermore, the effects of angiotensin I (AI) were studied to investigate the involvement of local angiotensin-I-converting enzyme (ACE) in adaptive responses. Ischemia was induced by partial occlusion of the left common iliac artery. Both in acute and chronic ischemia, the reactivity (maximal resistance change) of the vascular bed in the ischemic hindlimb to AI, AII and PE was increased only in severe ischemia (residual flow < 40%), whereas the sensitivity (ED50) was not influenced. The increase in reactivity was comparable for AI and AII, implying that local ACE seems not to be involved. These results suggest that severe ischemia of skeletal muscle results in nonselective hyperreactivity of the vascular bed, which may be due to alterations of receptor-linked mechanisms or ultrastructural changes of blood vessels.
Nelissen-Vrancken
H J
HJ
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
Leenders
P J
PJ
Struijker Boudier
H A
HA
Smits
J F
JF
D000208:Acute Disease; D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002908:Chronic Disease; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D014655:Vascular Resistance / Q000187:drug effects
D000804:Angiotensin II; D010656:Phenylephrine; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A