Endothelin-A Blockade Attenuates Systemic and Renal Hemodynamic Effects of L-NAME in Humans

Montanari, Alberto; A, Biggi; Carra, Nicoletta; Fasoli, Elena; Calzolari, Massimo; Corsini, Francesca; Perinotto, P; Novarini, A

doi:10.1161/01.hyp.35.1.518

Cited by 24 publications

(57 citation statements)

References 39 publications

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“…Doses of both drugs close to the ranges used in our experiments have been reported to produce in humans effective renal vasoconstriction with small systemic pressor changes for Ang II [27][28][29] and inhibition of systemic and renal effects of endogenous ET-1 for BQ, 19 respectively.…”

Section: Methodsmentioning

confidence: 53%

“…19 Variability for plasma PAH and inulin was 2.4% and 3.6%, respectively. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were estimated without measuring urinary PAH and inulin through the use of a constant-infusion technique.…”

Section: Calculationsmentioning

confidence: 94%

“…Plasma and infusate PAH and inulin were measured as previously described. 19 Plasma ET-1 was measured in extracted EDTA plasma samples with a commercially available immunoenzymatic method (R and D Systems).…”

Section: Methodsmentioning

confidence: 99%

“…The resulting infusion rate of PAH or inulin was divided for each measured plasma concentration, thus obtaining four clearance values at baseline and three in each infusion period. 19 The mean values were used in the expression of data for each period. Filtration fraction (FF) was calculated as the ratio between GFR and ERPF, renal blood flow (RBF) from ERPF, and hematocrit and renal vascular resistances (RVR) from MAP and RBF.…”

Section: Calculationsmentioning

confidence: 99%

“…In normal humans, systemic ET A blockade markedly blunts systemic and renal vasoconstriction as the result of either infusion of exogenous ET-1 [5][6][7] or to exogenous ET-1 left unopposed by NO synthesis inhibition. 19 However, the same doses of ET A antagonists produce only minor effects on systemic circulation and no changes in baseline renal hemodynamics. 6 -8,19 Under clinical conditions, in patients with disease characterized by marked activation of both the renin-angiotensin system (RAS) and the ET system, such as liver cirrhosis 20 and chronic heart failure (CHF), 21 systemic ET A blockade has been shown to produce vasodilation.…”

mentioning

confidence: 98%

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Endothelin-A Receptors Mediate Renal Hemodynamic Effects of Exogenous Angiotensin II in Humans

Montanari

Carra

et al. 2003

Hypertension

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Abstract-To investigate whether endothelin-A receptors mediate hemodynamic changes caused by exogenous Angiotensin II in humans, 7 healthy volunteers on a 250-mmol sodium diet underwent 3 separate p-aminohippurate and inulin-based renal hemodynamic studies. In 2 studies, Angiotensin II (increasing rates of 0.625, 1.25, and 2.5 ng/kg per minute, each for 30 minutes) was infused either alone or combined with endothelin-A blocker, BQ123, 0.4 nmol/kg per minute. A third infusion of BQ123 alone was not followed by any change. Key Words: receptors, endothelin Ⅲ angiotensin II Ⅲ kidney Ⅲ hemodynamics Ⅲ human A ngiotensin II (Ang II), a potent endogenous vasoconstricting and sodium-retaining peptide, plays a key role in the regulation of renal function and arterial pressure, 1,2 mostly by activating Ang II-type 1 (AT1) receptors, which leads to elevation in blood pressure, renal vasoconstriction, and sodium retention. Several of such actions are similar to those of endothelin-1 (ET-1), which is the predominant isoform of the endothelin family in human vasculature. 3,4 Vasoactive properties of ET-1 are mediated by two receptor subtypes, ET A and ET B , both leading to vasoconstriction in vascular smooth cells, whereas activation of ET B in endothelial cells causes vasodilation as the result of release of prostacyclin and nitric oxide (NO). 3,4 In humans, however, the ET A receptor is the main mediator of ET-1 renal vasoconstriction. 5-8 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 pathophysiological conditions. 3,4,9 -11 In most of these, interactions between Ang II and ET-1 may contribute largely to the observed changes. For instance, salt-sensitive hypertension, renal vasoconstriction, and cardiovascular and renal fibrotic damage, produced by chronic administration of exogenous Ang II, can be prevented by inhibition of endogenous ET-1, indicating that ET-1 mediates much of the vasoconstriction caused by chronic Ang II. 9 -11 Furthermore, ET-1 participates in the acute pressor effects of exogenous Ang II 12,13 and partly mediates the vasoconstriction from exogenous Ang II in different vascular beds, including kidney. 14,15 Interestingly, studies in rats have shown that such Ang II-ET-1 interaction may be sodium-dependent, because under elevated sodium intake, ET A blockade inhibited Ang II hypertension much more than under sodium restriction. 16 Ang II also stimulates both ET-1 synthesis and release, 3,4,17 whereas ET-1 enhances the pressor action of Ang II. 18 Finally, ET-1 and Ang II share the same intracellular signaling pathways. 3,17 Thus, ET-1 is generally considered as a powerful mediator of Ang II-dependent vasoconstriction and organ damage under experimental conditions. Conversely, little is known on the role of ET-1 and of its potential interactions with Ang II on systemic and renal hemodynamics in humans. In normal humans, systemic ET A blockade markedly blunts systemic and renal vasoconstr...

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