Antihypertensive therapy and adaptive mechanisms in peripheral ischemia.
In the present experiments the effect of long-term peripheral ischemia on the capillary of two hind limb skeletal muscles was investigated in spontaneously hypertensive rats. Furthermore, the effect of antihypertensive therapy on changes in capillarity and on the previously observed hyperreactivity of the ischemic vascular bed to vasoconstrictors was investigated in perfused hind limbs of rats after long-term treatment with the angiotensin I converting enzyme inhibitors captopril (0.5 mg/kg.h) or zabiciprilate (0.025 mg/kg.h), the angiotensin II type 1 receptor antagonist losartan (0.625 mg/kg.h), or the calcium antagonist felodipine (0.042 or 0.42 mg/kg.h). Skeletal muscle ischemia in the left hind limb was induced by partial ligation of the left common iliac artery. Long-term (4 weeks) ischemia increased significantly the capillary-to-fiber ratio in the soleus muscle, composed predominantly of type I fibers in spontaneously hypertensive rats, of the ischemic hind limb, whereas capillarity in the contralateral muscle was not affected. Furthermore, capillarity in the gastrocnemius muscle (type II muscle fiber part) of both the ischemic and contralateral hind limb did not change. Long-term treatment with the angiotensin I converting enzyme inhibitors during ischemia abolished the increase in the capillary-to-fiber ratio in the soleus muscle, whereas a comparable antihypertensive dose of felodipine had no effect. Greater blood pressure reductions by both losartan and felodipine prevented increases in capillarization in skeletal muscle ischemia. With respect to vascular hyperreactivity during ischemia, only treatment with losartan normalized reactivity of the ischemic vascular bed to vasoconstrictors.(ABSTRACT TRUNCATED AT 250 WORDS)
Nelissen-Vrancken
H J
HJ
Department of Pharmacology, University of Limburg, The Netherlands.
Boudier
H A
HA
Daemen
M J
MJ
Smits
J F
JF
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D002216:Captopril / Q000627:therapeutic use; D015736:Felodipine / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply; D007083:Iliac Artery; D007093:Imidazoles / Q000627:therapeutic use; D007511:Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D019808:Losartan; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D009132:Muscles / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR; D013777:Tetrazoles / Q000627:therapeutic use
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D007093:Imidazoles; D013777:Tetrazoles; C067839:zabiciprilat; D002216:Captopril; D019808:Losartan; D015736:Felodipine