Endothelin-1 attenuates bradykinin-induced hypotension in rats

Tanus‐Santos, José Eduardo; Gordo, Wladimir Mignone; Francisco-DoPrado, Joaquim; Sampaio, Rita; Moreno, Heitor

doi:10.1016/s0014-2999(00)00239-9

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…Previous studies suggested that ET-1 increases the responsiveness to norepinephrine and decreases the responsiveness to bradykinin, 34,35 although no change in responsiveness to norepinephrine was observed in another study. 30 The present study indicates that a lack of ET-1 in endothelial cells does not affect acute vascular responsiveness to exogenous ␣-adrenergic agonists or bradykinin.…”

Section: Responses To Vasoactive Substances In the Absence Of Endothementioning

confidence: 73%

Low Blood Pressure in Endothelial Cell–Specific Endothelin 1 Knockout Mice

et al. 2010

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Abstract-Endothelin (ET) 1 is a potent vasoconstrictor peptide produced by vascular endothelial cells and implicated in various pathophysiologic states involving abnormal vascular tone. Homozygous ET-1 null mice have craniofacial and cardiac malformations that lead to neonatal death. To study the role of ET-1 in adult vascular physiology, we generated a mouse strain (ET-1 flox/flox ;Tie2-Cre mice) in which ET-1 is disrupted specifically in endothelial cells. ET-1 peptide levels in plasma, heart, lung, kidney, and brain homogenates were reduced by 65% to 80% in these mice. mRNA levels for ET receptors were unaltered except that the ET A receptor mRNA was upregulated in the heart. ET-1 flox/flox ;Tie2-Cre mice had mean blood pressures 10 to 12 mm Hg lower than genetic controls. In contrast, the blood pressure of mice systemically heterozygous for the ET-1 null allele (ET-1 dlox/ϩ mice) was unchanged compared with wild-type littermates. Despite the lower basal blood pressure, acute pharmacological responses to angiotensin II, captopril, phenylephrine, bradykinin, N G -nitro-L-arginine methyl ester, and exogenous ET-1 were normal in ET-1 flox/flox ;Tie2-Cre mice. These results support an essential role of endothelial-derived ET-1 in the maintenance of basal vascular tone and blood pressure. Normal pharmacological responses of ET-1 flox/flox ;Tie2-Cre mice suggest that the renin-angiotensin system, the adrenergic system, and NO are not significantly altered by endothelial ET-1. Taken in conjunction with other lines of genetically altered mice, our results provide evidence for a paracrine vasoregulatory pathway mediated by endothelial cell-derived ET-1 acting on the vascular smooth muscle ET A receptor. (Hypertension. 2010;56:121-128.) Key Words: hypertension Ⅲ endothelium Ⅲ ET A Ⅲ ET B Ⅲ cre/loxP Ⅲ blood pressure Ⅲ gene knockout E ndothelin (ET) 1, originally identified as a potent vasoconstrictor derived from vascular endothelial cells, 1 is implicated in the pathogenesis of many cardiovascular disorders. 2,3 ET-1 is expressed by various cells during embryogenesis and in the adult under physiological and pathophysiologic conditions. 4 -6 However, the most abundant source of ET-1 in the adult animal is vascular endothelial cells. ET-1 acts on 2 distinct G protein-coupled receptors, termed ET A and ET B , 7,8 expressed in various vascular and nonvascular tissues. 9 Vascular smooth muscle cells express both ET A and ET B , which mediate a direct vasoconstrictor action of ET-1. Vascular endothelial cells express ET B , which exerts vasodilator effects via the release of NO and prostacyclin, and act as "clearance receptors" for circulating ET-1. The ET system also affects blood pressure via activity in renal collecting ducts, the brain, and the adrenal gland. The physiological function of ET-1 in the regulation of blood pressure is the subject of many pharmacological studies. 2,10 However, the relative contributions of ET A and ET B , as well as the overall physiological roles of endothelial ET-1 in the regulation of the...

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Section: Responses To Vasoactive Substances In the Absence Of Endothementioning

confidence: 73%

Low Blood Pressure in Endothelial Cell–Specific Endothelin 1 Knockout Mice

et al. 2010

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“…The decrease in ET 1 levels would be expected to lead to increased response to bradykinins, as ET 1 has been shown (in the rat) to attenuate the response to bradykinins. 49 Both valsartan and captopril reduced the levels of TBX 2 seen after injury and there was no significant difference between AT 1 -receptor blockade and ACE inhibition. Reduction was not complete and the influence of Ang II on TBX 2 levels in human mammary artery rings has been reported to be moderate or low.…”

Section: Discussionmentioning

confidence: 89%

Effect of valsartan and captopril in rabbit carotid injury. Possible involvement of bradykinin in the antiproliferative action of the renin-angiotensin blockade

Feng¹,

Ying²,

Hua³

et al. 2001

J Renin Angiotensin Aldosterone Syst

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The effects of the specific angiotensin II (Ang II) AT 1 -receptor blocker valsartan on events related to restenosis were investigated in rabbits after common carotid balloon injury. Six animals were given valsartan from two days prior to injury until 14 days post-injury. Three control groups (n=6 in each group) were either sham-operated, untreated or treated with the angiotensin-converting enzyme (ACE) inhibitor, captopril. Both ACE inhibition and AT 1 -receptor blockade had marked effects on plasma levels of endothelin ET 1 , thromboxane TXB 2 and 6-keto-PGF1-alpha. The most dramatic effects on ET 1 levels were seen in rabbits treated with valsartan, where levels were reduced to values close to those for sham-operated animals (96.85 vs. 86.45 pg/ml). Captopril treatment led to a statistically significant (p<0.01) reduction in ET 1 levels compared with untreated animals, but the reduction was only about half that seen with AT 1 -receptor blockade. TXB 2 levels doubled (202.58 vs. 413.28 pg/ml) upon arterial injury in control animals but rose by only 20-35% in rabbits treated with captopril (246.45 pg/ml) or valsartan (268.13). In untreated animals, 6-keto-PGF 1 -alpha levels decreased slightly after injury, but for both the captopril and valsartan groups, there were significant increases in levels of this prostaglandin derivative, effects attributed to the action of bradykinins. Levels were highest in the captopril-treated animals. Valsartan and captopril treatment led to a significant reduction in neointimal thickness and the extent of lumen stenosis compared with untreated animals. Both treatments were effective in reducing neointimal area and significantly (p<0.05) reduced cell proliferation. The differences between treatments can be attributed to the different actions of the agents, as valsartan leaves the AT 2 -receptor unblocked, while captopril, through inhibition of Ang II synthesis, prevents stimulation of both receptors. A combination of both treatments may be a possible way forward in the clinical prevention of restenosis. IntroductionPercutaneous transluminary angioplasty (PTCA) has revolutionised the treatment of angina pectoris in many ways and is today the most common invasive treatment of coronary heart disease (CHD).The opening of stenosed or occluded vessels through PTCA is successful in over 90% of cases.

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“…and the trachea was cannulated with a polyethylene tube (PE200). A polyethylene catheter (PE50) was inserted into the left carotid and the systemic blood pressure was recorded using a data acquisition system (MP150CE; Biopac Systems Inc., Goleta, CA, USA) connected to a computer (Acknowledge 3.2, for Windows) [18]. Another polyethylene catheter (PE10) was introduced into the right femoral vein for intravenous injections of drugs.…”

Section: Methodsmentioning

confidence: 99%

“…After baseline assessment of mean arterial pressure and heart rate for 15 min., all rats received saline followed by angiotensin I in doses of 0.03, 0.1, 0.3, 1, 3 and 10 lg ⁄ kg, followed by angiotensin II in doses of 0.01, 0.03, 0.1, 0.3, 1 and 3 lg ⁄ kg, and then bradykinin in doses of 0.03, 0.1, 0.3, 1, 3 and 10 lg ⁄ kg. These doses were chosen on the basis of our previous studies [14,18]. The changes in mean arterial pressure were calculated as the difference between the baseline value and those recorded at the highest values of mean arterial pressure after each dose of angiotensin I or angiotensin II, and as the difference between the baseline value and those recorded at the lowest values of mean arterial pressure after each dose of bradykinin.…”

Section: Methodsmentioning

confidence: 99%

Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro

Neto-Neves¹,

Montenegro²,

Dias‐Junior³

et al. 2010

Basic Clin Pharma Tox

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The precise mechanisms explaining the anti-hypertensive effects produced by quercetin are not fully known. Here, we tested the hypothesis that chronic quercetin treatment inhibits the angiotensin-converting enzyme (ACE). We examined whether quercetin treatment for 14 days reduces in vivo responses to angiotensin I or enhances the responses to bradykinin in anaesthetised rats. We measured the changes in systemic arterial pressure induced by angiotensin I in doses of 0.03-10 lg ⁄ kg, by angiotensin II in doses of 0.01-3 lg ⁄ kg, and to bradykinin in doses of 0.03-10 lg ⁄ kg in anaesthetised rats pre-treated with vehicle (controls), or daily quercetin 10 mg ⁄ kg intraperitoneally for 14 days, or a single i.v. dose of captopril 2 mg ⁄ kg. Plasma ACE activity was determined by a fluorometric method. Plasma quercetin concentrations were assessed by high performance liquid chromatography. Quercetin treatment induced no significant changes in the hypertensive responses to angiotensin I and angiotensin II, as well in the hypotensive responses to bradykinin (all p > 0.05). Conversely, as expected, a single dose of captopril inhibited the hypertensive responses to angiotensin I and potentiated the bradykinin responses (all p < 0.01), while no change was found in the vascular responses to angiotensin II (all p > 0.05). In addition, although we found significant amounts of quercetin in plasma samples (mean = 206 ng ⁄ mL), no significant differences were found in plasma ACE activity in rats treated with quercetin compared with those found in the control group (50 € 6 his-leu nmol ⁄ min ⁄ mL and 40 € 7 hisleu nmol ⁄ min ⁄ mL, respectively; p > 0.05). These findings provide strong evidence indicating that quercetin does not inhibit ACE in vivo or in vitro and indicate that other mechanisms are probably involved in the antihypertensive and protective cardiovascular effects associated with quercetin.Quercetin is the most abundant flavonoid found in the human diet and several beneficial cardiovascular effects have been ascribed to it, including improved endothelial function and cardiovascular protection [1][2][3][4]. Interestingly, quercetin increased nitric oxide bioavailability, improved vascular reactivity and produced antioxidant and antihypertensive effects in different experimental models of hypertension and in clinical hypertension [1,3,[5][6][7][8][9][10][11]. However, the precise mechanisms explaining the effects produced by quercetin are poorly known.The angiotensin-converting enzyme (ACE) is a key enzyme regulating the renin-angiotensin-aldosterone system, which plays a major role in the regulation of the cardiovascular function and blood pressure [12]. In this regard, flavonoids related to quercetin have been shown to inhibit angiotensin-converting enzyme in vitro and in vivo [13][14][15]. However, there is controversy with regard to the possible effects of quercetin on ACE. While Hackl et al. reported that quercetin acutely inhibits ACE [16], Actis-Goretta et al. showed that quercetin was unable to inhibit A...

show abstract

Endothelin-1 attenuates bradykinin-induced hypotension in rats

Cited by 7 publications

References 25 publications

Low Blood Pressure in Endothelial Cell–Specific Endothelin 1 Knockout Mice

Low Blood Pressure in Endothelial Cell–Specific Endothelin 1 Knockout Mice

Effect of valsartan and captopril in rabbit carotid injury. Possible involvement of bradykinin in the antiproliferative action of the renin-angiotensin blockade

Chronic Treatment with Quercetin does not Inhibit Angiotensin‐Converting Enzyme In Vivo or In Vitro

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