Increased Responsiveness of the Vascular Bed to Angiotensin I, Angiotensin II and Phenylephrine in Acute and Chronic Ischemic Hindlimbs in Rats

Nelissen-Vrancken, H. J. M. G.; Leenders, Peter; Boudier, Struijker; Smits, J. F. M.

doi:10.1159/000158952

Cited by 7 publications

(11 citation statements)

References 17 publications

(25 reference statements)

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“…The data indicate that a unilateral partial ligation of the common iliac artery in the rat, which causes a flow reduction of more than 60%, 5 results in an increase in capillarity predominantly in the slow oxidative (type I muscle fiber) soleus muscle. Furthermore, the reninangiotensin system seems to be involved in the neovascularization in soleus muscle and in the previously observed nonselective hyperreactivity to vasoconstrictors.…”

Section: Therapymentioning

confidence: 89%

“…Long-term ischemia was induced by partial ligation of the left common iliac artery with rats under ether anesthesia. 5 The abdomen was opened, and the left common iliac artery was dissected. Partial occlusion of the artery was accomplished by firmly tying a stainless steel wire (0.15 mm) against the side of the vessel with a 4-0 silk suture, resulting in complete occlusion of the vessel lumen.…”

Section: Surgery and Preparationsmentioning

confidence: 99%

“…Ischemic hind limbs with a residual flow greater than 40% do not have an increased reactivity of the vasculature. 5 Therefore, only animals with a residual left flow less than 40% were used. The capillary-to-fiber ratio (C/F) was computed from the numbers of capillaries and fibers.…”

Section: ±7mentioning

confidence: 99%

“…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. 7 One of the mechanisms for restoring blood supply to the ischemic regions is the development of collateral vessels.…”

mentioning

confidence: 99%

“…Therefore, in the present experiments the effect of long-term (4 weeks) ischemia of skeletal muscle on capillarity in the soleus muscle (oxidative fibers) and in the type II muscle fiber part (glycolytic and oxidative glycolytic fibers) of the gastrocnemius muscle was investigated. Also, the influence of ACE inhibition, Ang II antagonism, and calcium antagonism on possible capillarity changes in ischemic and nonischemic skeletal muscles and their influence on the previously described nonselective hyperreactivity of the vascular bed of ischemic hind limbs to vasoconstrictors 5 were investigated. Spontaneously hypertensive rats with induced skeletal muscle ischemia were chronically treated (4 weeks) with the ACE inhibitors captopril and zabiciprilate, the Ang II type 1 (AT,) receptor antagonist losartan, or the calcium antagonist felodipine.…”

mentioning

confidence: 99%

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Antihypertensive therapy and adaptive mechanisms in peripheral ischemia.

Nelissen-Vrancken¹,

Boudier²,

Daemen³

et al. 1993

Hypertension

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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

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Section: Therapymentioning

confidence: 89%

Section: Surgery and Preparationsmentioning

confidence: 99%

Section: ±7mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Antihypertensive therapy and adaptive mechanisms in peripheral ischemia.

Nelissen-Vrancken¹,

Boudier²,

Daemen³

et al. 1993

Hypertension

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

et al. 2013

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Analysis of global gene expression in mesenteric control and collateral arteries was used to investigate potential molecules, pathways, and mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive Rat (SHR). A fundamental difference was observed in overall gene expression pattern in SHR versus Wistar Kyoto (WKY) collaterals; only 6% of genes altered in collaterals were similar between rat strains. Ingenuity® Pathway Analysis (IPA) identified major differences between WKY and SHR in networks and biological functions related to cell growth and proliferation and gene expression. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were downregulated including JUN (−5.2×, P = 0.02), EGR1 (−4.1×, P = 0.01), and NFĸB1 (−1.95×, P = 0.04). Predicted binding sites for NFĸB and AP-1 were present in genes altered in WKY but not SHR collaterals. Immunostaining showed increased NFĸB nuclear translocation in collateral arteries of WKY and apocynin-treated SHR, but not in untreated SHR. siRNA for the p65 subunit suppressed collateral growth in WKY, confirming a functional role of NFkB. Canonical pathways identified by IPA in WKY but not SHR included nitric oxide and renin–angiotensin system signaling. The angiotensin type 1 receptor (AGTR1) exhibited upregulation in WKY collaterals, but downregulation in SHR; pharmacological blockade of AGTR1 with losartan prevented collateral luminal expansion in WKY. Together, these results suggest that collateral growth impairment results from an abnormality in a fundamental regulatory mechanism that occurs at a level between signal transduction and gene transcription and implicate redox-dependent modulation of mechano-sensitive transcription factors such as NFĸB as a potential mechanism.

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