Angiotensin II receptor blockade unmasks a depressor response to endothelin antagonists in rats

Richard, Vincent; Hogie, Manuela; Thuillez, Christian

doi:10.1111/j.1472-8206.2000.tb00397.x

Cited by 11 publications

(9 citation statements)

References 16 publications

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“…Therefore, our data suggest that an increased vasoconstrictor effect of ET limits the systemic vasodilation induced by AT 1 blockade. These observations are corroborated by findings in dogs of either sex (8) and male rats (31), in which combined blockade of ET A /ET B and AT 1 receptors resulted in decreases in SVR and aortic blood pressure that were larger than the sum of the decreases produced by individual blockade of either ET A /ET B or AT 1 receptors alone. Interestingly, the decreases in blood pressure induced by combined blockade ET A /ET B or AT 1 receptors in these studies are larger than those observed in the present study, which may have been due to the presence of pentobarbital anesthesia.…”

Section: Integrated Regulation Of Resistance Vessel Tone By Et and Ansupporting

confidence: 76%

“…In contrast to the ET-stimulating effects of exogenous ANG II, endogenous ANG II appears to suppress the ET system. Thus, in anesthetized rats (31) and dogs (8), combined blockade of ET A /ET B and AT 1 receptors resulted in a decrease in SVR that was larger than the sum of the decreases in SVR produced by individual ET A /ET B and AT 1 blockade. These observations could be interpreted to suggest that the lack of effect of AT 1 blockade on PVR previously reported in swine (3) and dogs (8) may have been due to a concomitant increased ET vasoconstrictor influence.…”

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confidence: 99%

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Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender

Beer

Graaff

Hoekstra

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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de Beer VJ, de Graaff HJ, Hoekstra M, Duncker DJ, Merkus D. Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender. Am J Physiol Heart Circ Physiol 298: H1976 -H1985, 2010. First published March 26, 2010 doi:10.1152/ajpheart.00459.2009The lungs are now recognized as an active metabolic organ that is a major determinant of the plasma concentrations of the vasoconstrictors endothelin (ET) and ANG II. Several studies have suggested a complex interaction between ET and ANG II in the systemic and coronary vascular beds that is different at rest and during exercise. To date, the interaction between these vasoconstrictor peptides has barely been investigated in relation to the pulmonary vascular bed. Consequently, we investigated the integrated control of pulmonary vasomotor tone by ET and ANG II in 24 chronically instrumented swine (15 female and 9 male) at rest and during graded treadmill exercise. In the systemic circulation, ANG II type 1 (AT1) receptor blockade with irbesartan and mixed ET A/ETB blockade with tezosentan each produced vasodilation. The systemic vasodilator effect of ETA/ETB blockade was enhanced after AT1 blockade in female swine, whereas a trend toward an increase was observed in male swine. In the pulmonary circulation, AT1 receptor blockade had no effect on pulmonary vascular tone in male swine, whereas it resulted in an unexpected increase in pulmonary vasomotor tone in female swine. ETA/ETB receptor blockade did not result in a decrease in pulmonary vasomotor tone at rest but produced a decrease in vasomotor tone during exercise in both genders. This pulmonary vasodilation by ETA/ETB receptor blockade was enhanced after prior AT1 blockade in female swine but not in male swine. In conclusion, in both the systemic and pulmonary circulation of female swine, ANG II inhibits the vasoconstrictor influence of ET. This interaction is gender specific. The observation that plasma ET levels were not altered by AT1 blockade in either gender suggests that the interaction between these vasoconstrictors occurs locally in the vasculature. microcirculation; exercise DURING EXERCISE, systemic vascular resistance (SVR) decreases by 70 -80% as a result of vasodilation of the exercising skeletal muscle. In contrast to the substantial decrease in SVR, pulmonary vascular resistance (PVR) decreases only modestly (20 -40%) during exercise (20). Consequently, the marked increase in cardiac output together with a small increase in left atrial pressure results in a significant increase in pulmonary arterial pressure, which serves to increase the homogeneity of pulmonary perfusion during exercise, thereby improving lung gas exchange (20,29). In addition to its obvious role in gas exchange, the lungs are increasingly recognized as an active metabolic organ contributing to the production and degradation of many vasoactive peptides. Two of such peptides that are produced and/or metabolized by the lungs are endothelin (ET) and ANG II. ET B receptors in the lungs m...

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Section: Integrated Regulation Of Resistance Vessel Tone By Et and Ansupporting

confidence: 76%

mentioning

confidence: 99%

Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender

Beer

Graaff

Hoekstra

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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“…It is well known that the regulation of arterial tone is complex and involves numerous neuronal, endocrine, and autacoid interactions. It has recently been demonstrated that blockade of the renin-angiotensin system unmasks a potent vasodilatory response to ET antagonists in normotensive anesthetized rats (29). The authors conclude that this suggests that endogenous ET-1 indeed contributes to the normal vasodepressor tone and that this contribution may be evidenced after blockade of the reninangiotensin system.…”

Section: Table 3 Effect Of Et Antagonists On the Et-1-induced Attenumentioning

confidence: 72%

Endothelin-induced modulation of neuropeptide Y and norepinephrine release from the rat mesenteric bed

Hoang

Macarthur

Gardner

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Endothelin-induced modulation of neuropeptide Y and norepinephrine release from the rat mesenteric bed. Am J Physiol Heart Circ Physiol 283: H1523-H1530, 2002. First published June 20, 2002 10.1152/ ajpheart.00177.2001.-The effect of three endothelin (ET) agonists [ET-1, ET-3, and sarafotoxin (STX6C)] on the nerve stimulation-induced release of norepinephrine (NE) and neuropeptide Y-immunoreactive compounds (NPY-ir) from the perfused mesenteric arterial bed of the rat as well as the effect on perfusion pressure were examined. ET-1, ET-3, and STX6C all produced a significant, concentration-dependent decrease in the evoked release of NPY-ir but had no effect on the release of NE. In contrast, all three ETs potentiated the nerve stimulation-induced increase in perfusion pressure. The inhibition of nerve stimulation-induced NPY-ir release by ET-1 was significantly blocked by the ET A/ETB antagonist PD-142893 and the ET B antagonist RES-701-1 but not by the ET A antagonist BQ-123. The potentiation of the nerve stimulation-induced increase in perfusion pressure by ET-1 was significantly blocked by PD-142893 and BQ-123 and attenuated by RES-701-1. Prior exposure of the preparation to indomethacin or meclofenamate failed to alter the attenuation of the evoked release of NPY-ir or the potentiation of the increase in perfusion pressure produced by ET-1 or ET-3. These results are consistent with the idea that sympathetic cotransmitters can be preferentially modulated by paracrine mediators at the vascular neuroeffector junction. sympathetic neurotransmission ENDOTHELINS (ETs) are a family of 21-amino acid peptides that consist of at least three isoforms encoded by distinct genes, ET-1, ET-2, and ET-3 (5, 44). The three ETs possess a spectrum of biological activities including both vasodilation and vasoconstriction (38, 44). There appear to be at least three major subtypes of receptors, including ET A , ET B , and ET C , with a further classification into ET A1 , ET A2 , ET B1 , and ET B2 (5,9,14). The suggestion has been made that ETs can exert a modulatory effect on the release of various neurotransmitters from sympathetic neurons or other perivascular nerves. ET-1 has been suggested to attenuate sympathetic neurotransmission, whereas it enhances the contractile response to exogenous norepinephrine (NE) in a variety of isolated vascular or nonvascular smooth muscle preparations (22,31,32,34,41). A similar ET-1-induced decrease in the transmural nerve stimulation-evoked release of ACh and an enhancement of the contractile response to ACh in the guinea pig ileum has also been reported (42). Moreover, ETs have been demonstrated to enhance the contractile effect induced by nerve stimulation or by various vasoactive agents (17,32,33,43).Considerable evidence suggests that sympathetic neurons innervating the vascular smooth muscle contain at least three chemical mediators, including NE, neuropeptide Y (NPY), and ATP (21, 26). A question of major importance is what regulates the release of these cotransmitters and whether or ...

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“…8,16 Even when selective ET A blockade has been performed by infusing drugs locally in the forearm of normal subjects, conflicting results have been obtained, ranging from no changes 17 to a 40% increase in baseline blood flow. 18 On the other hand, studies in both normal dogs and rats undergoing simultaneous systemic blockade of renin-angiotensin system (RAS) with either ACE inhibitors (ACEI) 4,5 or AT 1 receptor antagonists (AIIRA) 19 have shown that hypotension and, primarily, marked renal vasodilation resulted from ET A or mixed ET A /ET B blockade. For instance, Berthold et al 4,5 have reported that, in dogs receiving both ACEI trandolapril and ET A blocker LU135252, renal blood flow (RBF) increased to an extent 3 to 4 times larger than that observed with ET A blockade alone.…”

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confidence: 99%

Renal Hemodynamic Control by Endothelin and Nitric Oxide Under Angiotensin II Blockade in Man

et al. 2002

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Abstract-To investigate whether endothelin-A receptors and nitric oxide modulate renal hemodynamics in man under angiotensin II receptor-1 blockade, 6 healthy volunteers, on a 240 mmol Na diet, underwent 4 separate renal hemodynamic measurements, in 3 of which endothelin-A blocker BQ-123 0.2 nmol ⅐ kg ⅐ min Ϫ1 was infused for 90 minutes after pretreatment with either placebo, telmisartan 1 mg ⅐ kg ⅐ day Ϫ1 for 3 days, or telmisartan as well, but with co-infusion of both BQ-123 and N G -nitro-L-arginine methylester 0.5 g ⅐ kg ⅐ min Ϫ1 . A fourth infusion was made with N G -nitro-L-arginine methylester alone. No change followed infusion of either N G -nitro-L-arginine methylester alone or BQ-123 alone. With BQ-123 after telmisartan, renal blood flow rose from 916Ϯ56 mL ⅐ min Ϫ1 ⅐ 1.73 m 2 to 1047Ϯ51.2 (PϽ0.001), and renal vascular resistances fell from 89Ϯ7 mm Hg ⅐ min ⅐ L Ϫ1 to 74Ϯ4 (PϽ0.001). These changes were fully abolished by the co-infused N G -nitro-L-arginine methylester. Infusion of BQ-123, devoid of renal hemodynamic effects at baseline, produces significant renal vasodilation when angiotensin II receptors are blocked, indicating an increasing renal hemodynamic role of endothelin-A-receptor activity. Because such a vasodilation is prevented by nonvasoconstricting microdoses of N G -nitro-L-arginine methylester, nitric oxide-endothelin balance controls substantially renal hemodynamics under angiotensin II blockade. These findings are consistent with a rationale of the association of endothelin-A blockers with angiotensin II blockers or angiotensin-converting enzyme inhibitors in treating nitric oxide-deficient conditions such as arterial hypertension, heart failure, and chronic renal diseases. Key Words: angiotensin II Ⅲ nitric oxide Ⅲ endothelin Ⅲ kidney Ⅲ hemodynamics Ⅲ L-NAME Ⅲ receptors, endothelin H emodynamic control in both systemic circulation and kidney results physiologically from a balance of opposing vasodilator systems such as nitric oxide (NO) and prostaglandins, and vasoconstrictor systems. 1 These latter include, besides sympathetic nervous system, the 2 potent peptide vasoconstrictors angiotensin II (Ang II) and endothelin-1 (ET-1), 1 this latter being the predominant isoform of endothelin family expressed in human vasculature. 2 Vasoactive properties of ET-1 are mediated by 2 receptor subtypes, ET A and ET B , both leading to vasoconstriction in vascular smooth muscle cells, whereas activation of ET B in endothelial cells may cause vasodilation through the release of prostacyclin and NO. 2,3 At the kidney level, however, studies in both dogs 4,5 and humans 6,7,8 have indicated the ET A receptor as the main mediator of the vasoconstrictor effect of ET-1.A considerable body of evidence has shown that ET-1, although it is the most potent endogenous vasoconstrictor, assumes a major hemodynamic role and contributes to the end-organ damage, mainly under experimental and clinical pathophysiological conditions. 2,3 Furthermore, a number of interactions have been recognized between Ang II and ET...

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Angiotensin II receptor blockade unmasks a depressor response to endothelin antagonists in rats

Cited by 11 publications

References 16 publications

Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender

Integrated control of pulmonary vascular tone by endothelin and angiotensin II in exercising swine depends on gender

Endothelin-induced modulation of neuropeptide Y and norepinephrine release from the rat mesenteric bed

Renal Hemodynamic Control by Endothelin and Nitric Oxide Under Angiotensin II Blockade in Man

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