Antihypertensive therapy and adaptive mechanisms in peripheral ischemia.

Abstract

In the present experiments the effect of long-term peripheral ischemia on the capillarity 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. These data suggest that both the renin-angiotensin system, probably through the angiotensin II type 1 receptor, and hypoperfusion play a role in the adaptation mechanisms after ischemia of skeletal muscle. and metabolic and structural adaptations of skeletal muscles. 3 '' In a rat model for long-term ischemia of skeletal muscle, we previously demonstrated hyperreactivity of the total vascular bed of severely ischemic hind limbs to the vasoconstrictors angiotensin I (Ang I), angiotensin II (Ang II), and phenylephrine, 5 whereas in a comparable ischemia model Verheyen and coworkers observed a hyperreactivity to serotonin 6 and a thromboxane analogue. One of the mechanisms for restoring blood supply to the ischemic regions is the development of collateral vessels. 8 -9 Generation of new vessels has been described in relative hypoxic (increased oxygen demand) and hypoxic situations after endurance training 10 "; similar observations were made after long-term electrical stimulation of skeletal muscles 12 and in ischemia of skeletal

Angiogenesis and hypertension: an update

“…94 Captopril reduced microvascular growth in hypertensive and normotensive rats 95 and the capillary-fibre ratio in ischaemic hind limbs of rats. 96 ACE-Is, which differ from captopril chemically, however, do not possess these specific anti-angiogenic properties.…”

Molecular basis for impaired collateral artery growth in the spontaneously hypertensive rat: insight from microarray analysis

“…) and is documented to have impaired compensation to arterial occlusion in the peripheral circulation including the mesentery and hindlimb (Nelissen‐Vrancken et al. , ; Scheidegger et al. ; Emanueli et al.…”

“…The current study was undertaken to identify potential mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR), an animal model widely utilized to assess vascular adaptations to peripheral arterial occlusion (Nelissen‐Vrancken et al. , ; Scheidegger et al. ; Emanueli et al.…”

“…The current study was undertaken to identify potential mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR), an animal model widely utilized to assess vascular adaptations to peripheral arterial occlusion (Nelissen-Vrancken et al 1992, 1993Scheidegger et al 1997;Emanueli et al 2001Emanueli et al , 2002Tamarat et al 2002;Tuttle et al 2002b;Srivastava et al 2003;Iaccarino et al 2005;Miller et al 2007a;You et al 2008;Matsumura et al 2009). Microarray analysis of control and collateral mesenteric arteries was performed and the results demonstrate a fundamental difference in the overall collateral gene expression pattern in SHR versus normotensive control rats (Wistar Kyoto; WKY).…”

The Capillary Pattern in Human Masseter Muscle During Ageing

“…Further, the ratio of capillary profiles to fibres was significantly larger in those muscles that exhibited a significantly larger proportion of oxidative fibre types (Cui et al, 2008), while the number of capillary profiles per muscle cross-sectional area was larger in type 1 muscle fibres than in type 2 muscle fibres; i.e., on average, in the oxidative muscle there are more capillary profiles per fibre compared to glycolytic muscle (Nelissen-Vrancken et al, 1993). Long-term (4 weeks) ischemia increased significantly the capillary-to-fibre ratio in the soleus muscle, composed predominantly of type 1 fibres, whereas capillarity in the more glycolytic portion of the gastrocnemius muscle did not change.…”