Participation of kinins in the captopril‐induced inhibition of intimal hyperplasia caused by interruption of carotid blood flow in the mouse

Emanueli, Costanza; Salis, Maria Bonaria; Figueroa, Carlos D.; Chao, Julie; Chao, Lee; Gaspa, Leonardo; Capogrossi, Maurizio C.; Madeddu, Paolo

doi:10.1038/sj.bjp.0703388

Cited by 11 publications

(10 citation statements)

References 37 publications

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“…However, proangiogenic activity is not unique to ANG II. ACE inhibitors, HOE140, or the absence of the BKB2R results in reduced intimal hyperplasia produced by interrupted carotid blood flow in mice (41). These data, along with evidence that ACE inhibitors increased vessel density and capillary number in a model of surgically induced hindlimb ischemia in wild-type but not BKB2R Ϫ/Ϫ mice indicate that the BKB2R mediates the proangiogenic effect of these drugs (121).…”

Section: The Interaction Of the Plasma Kks And Ras In Angiogenesismentioning

confidence: 80%

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

Schmaier

2003

American Journal of Physiology-Regulatory, Integrative and Comp

150

127

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Understanding the physiological role of the plasma kallikrein-kinin system (KKS) has been hampered by not knowing how the proteins of this proteolytic system, when assembled in the intravascular compartment, become activated under physiological conditions. Recent studies indicate that the enzyme prolylcarboxypeptidase, an ANG II inactivating enzyme, is a prekallikrein activator. The ability of prolylcarboxypeptidase to act in the KKS and the renin-angiotensin system (RAS) indicates a novel interaction between these two systems. This interaction, along with the roles of angiotensin converting enzyme, cross talk between bradykinin and angiotensin-(1-7) action, and the opposite effects of activation of the ANG II receptors 1 and 2 support a hypothesis that the plasma KKS counterbalances the RAS. This review examines the interaction and cross talk between these two protein systems. This analysis suggests that there is a multilayered interaction between these two systems that are important for a wide array of physiological functions.

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Section: The Interaction Of the Plasma Kks And Ras In Angiogenesismentioning

confidence: 80%

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

Schmaier

2003

American Journal of Physiology-Regulatory, Integrative and Comp

150

127

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“…After the unexpected results with losartan, additional experiments were performed to clarify the mechanisms by which captopril, but not losartan, promoted collateral growth. ACEI can influence remodeling events by their effect on the kallikrein-kinin system and stimulation of NO production (15). The sulfhydryl group within captopril endows it with antioxidant properties (38) not found in most ACEI.…”

Section: Resultsmentioning

confidence: 99%

The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

Miller

Norton

Murphy³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.

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“…Previous studies of intima formation in the mouse carotid after ligation showed no effect of B 1 R or B 2 R antagonists on intima. 35 In cultured VSMCs, bradykinin was shown to both stimulate 36 and inhibit growth. 23 The fact that blocking either B 1 R or B 2 R abrogated the ability of valsartan to limit intima formation is somewhat surprising, especially because blockade did not decrease AT 2 R expression.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Type 2 Receptor Expression After Vascular Injury

et al. 2006

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Abstract-It has been suggested that the effects of angiotensin II type 1 receptor (AT 1 R) blockers are in part because of angiotensin II type 2 receptor (AT 2 R) signaling. Interactions between the AT 2 R and kinins modulate cardiovascular function. Because AT 2 R expression increases after vascular injury, we hypothesized that the effects on vascular remodeling of the AT 1 R blocker valsartan and the ACE inhibitor benazepril require AT 2 R signaling through the bradykinin 1 and 2 receptors (B 1 R and B 2 R). To test this hypothesis, Brown Norway rats were assigned to 8 treatments (nϭ16): valsartan, valsartanϩPD123319 (AT 2 R inhibitor), valsartanϩdes-arg 9 -[Leu 8 ]-bradykinin (B 1 R inhibitor), valsartanϩHOE140 (B 2 R inhibitor), benazepril, benazeprilϩHOE140, amlodipine, and vehicle. After 1 week of treatment, carotid balloon injury was performed. Two weeks later, carotids were harvested for morphometry and analysis of receptor expression by immunohistochemistry and Western blotting. Valsartan and benazepril significantly reduced the intima:media ratio compared with vehicle. Blockade of AT 2 R, B 1 R, or B 2 R in the presence of valsartan prevented the reduction seen with valsartan alone. B 2 R blockade inhibited the effect of benazepril. Injury increased AT 1 R, AT 2 R, B 1 R, and B 2 R expression. Treatment with valsartan but not benazepril significantly increased intima AT 2 R expression 2-fold compared with vehicle, which was not reversed by inhibition of AT 2 R, B 1 R, and B 2 R. Functionally, valsartan increased intimal cGMP levels compared with vehicle, and this increase was inhibited by blocking the AT 2 R, B 1 R, and B 2 R. Results suggest that AT 2 R expression and increased cGMP represent a molecular mechanism that differentiates AT 1 R blockers, such as valsartan, from angiotensin-converting enzyme inhibitors like benazepril. Key Words: valsartan Ⅲ angiotensin Ⅲ AT 2 R Ⅲ restenosis Ⅲ rat A ngiotensin II (Ang II) exerts its effects primarily through 2 functionally distinct receptors, the angiotensin type 1 receptor (AT 1 R) and angiotensin type 2 receptor (AT 2 R). The AT 1 R is widely distributed in adults, whereas the AT 2 R is only highly expressed in the fetus. 1 However, AT 2 R expression increases in pathological conditions, such as vascular injury. 2 These 2 receptors exert effects that are generally considered antagonistic. Blocking Ang II activity with angiotensin-converting enzyme (ACE) inhibitors reduces the risk of mortality in patients at high risk for cardiovascular events. 3 Recently, AT 1 R blockers (ARBs) have been shown to be effective in reducing stroke in patients with left ventricular hypertrophy 4 and mortality in heart failure patients. 5 Kinins exert diverse physiological actions, including vasodilation, 6 increased capillary permeability, and inflammation. 7 The major kinins, which are agonists at the bradykinin type 2 receptor (B 2 R), are metabolized to produce the des-Arg 9 -kinins, which are agonists at bradykinin type 1 receptors (B 1 Rs). Although the B 2 R is widely...

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Participation of kinins in the captopril‐induced inhibition of intimal hyperplasia caused by interruption of carotid blood flow in the mouse

Cited by 11 publications

References 37 publications

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

The kallikrein-kinin and the renin-angiotensin systems have a multilayered interaction

The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment

Angiotensin II Type 2 Receptor Expression After Vascular Injury

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