Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA<sub>2</sub>/isoprostane production

Vågnes, Øyvind; Iversen, Bjarne M.; Arendshorst, William J.

doi:10.1152/ajprenal.00510.2006

Cited by 12 publications

(7 citation statements)

References 55 publications

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“…Previous studies in a sheep model (50) did not observe any difference in systemic MAP with a short infusion of considerably higher doses of ANG II into the renal artery, suggesting that there is little spillover into the systemic circulation. This is consistent with observations that the kidney clears a large proportion of ANG II (33,40,54) and with the very modest increase in plasma levels of ANG II during the peptide infusions (discussed below).…”

Section: Discussionsupporting

confidence: 91%

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Contag

Bi²,

Chappell

et al. 2010

American Journal of Physiology-Renal Physiology

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Antenatal corticosteroids may have long-term effects on renal development which have not been clearly defined. Our objective was to compare the responses to intrarenal infusions of ANG II in two groups of year-old, male sheep: one group exposed to a clinically relevant dose of betamethasone before birth and one not exposed. We wished to test the hypothesis that antenatal steroid exposure would enhance renal responses to ANG II in adult life. Six pairs of male sheep underwent unilateral nephrectomy and renal artery catheter placement. The sheep were infused for 24 h with ANG II or with ANG II accompanied by blockade of the angiotensin type 1 (AT(1)) or type 2 (AT(2)) receptor. Baseline mean arterial blood pressure among betamethasone-exposed sheep was higher than in control animals (85.8 +/- 2.2 and 78.3 +/- 1.0 mmHg, respectively, P = 0.003). Intrarenal infusion of ANG II did not increase systemic blood pressure (P >/= 0.05) but significantly decreased effective renal plasma flow and increased renal artery resistance (P < 0.05). The decrease in flow and increase in resistance were significantly greater in betamethasone- compared with vehicle-exposed sheep (betamethasone P < 0.05, vehicle P >/= 0.05). This effect appeared to be mediated by a heightened sensitivity to the AT(1) receptor among betamethasone-exposed sheep. Sodium excretion initially decreased in both groups during ANG II infusion; however, a rebound was observed after 24 h. AT(1) blockade was followed by a significant rebound after 24 h in both groups. AT(2) blockade blunted the 24-h rebound effect among the vehicle-exposed sheep compared with the betamethasone-exposed sheep. In conclusion, antenatal corticosteroid exposure appears to modify renal responsiveness to ANG II by increasing AT(1)- and decreasing AT(2) receptor-mediated actions particularly as related to renal blood flow and sodium excretion.

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Section: Discussionsupporting

confidence: 91%

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Contag

Bi²,

Chappell

et al. 2010

American Journal of Physiology-Renal Physiology

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“…ANG II also promotes the renal production of TxA 2 , which, in turn, causes renal vasoconstriction (177). The effects of ANG II on multiple systems and vascular mediators may explain the elevated BP in essential and renovascular HTN where the ANG II levels may be normal (133).…”

Section: Renal Endothelial Cell Dysfunction In Htnmentioning

confidence: 99%

Cellular mediators of renal vascular dysfunction in hypertension

Ponnuchamy¹,

Khalil²

2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Ponnuchamy B, Khalil RA. Cellular mediators of renal vascular dysfunction in hypertension. Am J Physiol Regul Integr Comp Physiol 296: R1001-R1018, 2009. First published February 18, 2009 doi:10.1152/ajpregu.90960.2008.-The renal vasculature plays a major role in the regulation of renal blood flow and the ability of the kidney to control the plasma volume and blood pressure. Renal vascular dysfunction is associated with renal vasoconstriction, decreased renal blood flow, and consequent increase in plasma volume and has been demonstrated in several forms of hypertension (HTN), including genetic and salt-sensitive HTN. Several predisposing factors and cellular mediators have been implicated, but the relationship between their actions on the renal vasculature and the consequent effects on renal tubular function in the setting of HTN is not clearly defined. Gene mutations/ defects in an ion channel, a membrane ion transporter, and/or a regulatory enzyme in the nephron and renal vasculature may be a primary cause of renal vascular dysfunction. Environmental risk factors, such as high dietary salt intake, vascular inflammation, and oxidative stress further promote renal vascular dysfunction. Renal endothelial cell dysfunction is manifested as a decrease in the release of vasodilatory mediators, such as nitric oxide, prostacyclin, and hyperpolarizing factors, and/or an increase in vasoconstrictive mediators, such as endothelin, angiotensin II, and thromboxane A 2. Also, an increase in the amount/activity of intracellular Ca 2ϩ concentration, protein kinase C, Rho kinase, and mitogenactivated protein kinase in vascular smooth muscle promotes renal vasoconstriction. Matrix metalloproteinases and their inhibitors could also modify the composition of the extracellular matrix and lead to renal vascular remodeling. Synergistic interactions between the genetic and environmental risk factors on the cellular mediators of renal vascular dysfunction cause persistent renal vasoconstriction, increased renal vascular resistance, and decreased renal blood flow, and, consequently, lead to a disturbance in the renal control mechanisms of water and electrolyte balance, increased plasma volume, and HTN. Targeting the underlying genetic defects, environmental risk factors, and the aberrant renal vascular mediators involved should provide complementary strategies in the management of HTN. blood pressure; dietary salt; oxidative stress; cytokines; kidney; endothelium; vascular smooth muscle; extracellular matrix; matrix metalloproteinases THE ROLE OF THE KIDNEY IN the regulation of sodium and water balance and blood pressure (BP) is well recognized (53,55,128). A decrease in plasma volume and renal blood flow (RBF) stimulates renin release from the juxtaglomerular cells (JGCs) and activates the renin-angiotensin system (RAS). Renin transforms angiotensinogen to angiotensin I (ANG I), and angiotensin-converting enzyme (ACE) transforms ANG I to ANG II. ANG II stimulates the adrenal cortex to release aldosterone (Aldo), which acts on the rena...

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“…However, the detailed mechanisms responsible for this finding are still to be clarified. However, TXA 2 , a powerful vasoconstrictor, is suggested to play a causative role in the pathogenesis of hypertension (15, 16), and its production is elevated in hypertension as a result of stimulation by angiotensin II (Ang II) (17). Thus, if selective inhibition of TP receptor-mediated contractions by DHA is not limited to guinea-pig blood vessels and is a common phenomenon attained in all blood vessels, the possible circulatory-protective effects of ω-3 PUFAs including DHA may be strengthened with further experimental evidence obtained from a different preparation from another species.…”

Section: Introductionmentioning

confidence: 99%

Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619-induced contraction in rat aorta

Sato

Chino

Kobayashi

et al. 2013

J. Smooth Muscle Res.

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Inhibitory effects of docosahexaenoic acid (DHA) on blood vessel contractions induced by various constrictor stimulants were investigated in the rat thoracic aorta. The inhibitory effects of DHA were also compared with those of eicosapentaenoic acid (EPA) and linoleic acid (LA). DHA exhibited a strong inhibitory effect on the sustained contractions induced by U46619, a TXA2 mimetic. This inhibitory effect of DHA was not affected by removal of the endothelium or by treatment with either indomethacin or Nω-nitro-l-arginine. DHA also significantly diminished PGF2α-induced contraction but did not show any appreciable inhibitory effects on the contractions to both phenylephrine (PE) and high-KCl. Similarly, EPA exhibited significant inhibitory effects against the contractions induced by both U46619 and PGF2α without substantially affecting either PE- or high-KCl-induced contractions. However, both DHA and EPA generated more potent inhibitions against contractions induced by U46619 than those by PGF2α. In contrast, LA did not show significant inhibitory effects against any contractions, including those induced by U46619. The present findings suggest that DHA and EPA elicit more selective inhibition against blood vessel contractions that are mediated through stimulation of prostanoid receptors than those through α-adrenoceptor stimulation or membrane depolarization. Although DHA and EPA have similar inhibitory potencies against prostanoid receptor-mediated contractions, they had a more potent inhibition against TXA2 receptor (TP receptor)-mediated contractions than against PGF2α receptor (FP receptor)-mediated responses. Selective inhibition by either DHA or EPA of prostanoid receptor-mediated blood vessel contractions may partly underlie the mechanisms by which these ω-3 polyunsaturated fatty acids exert their circulatory-protective effects.

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Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA₂/isoprostane production

Cited by 12 publications

References 55 publications

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Cellular mediators of renal vascular dysfunction in hypertension

Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619-induced contraction in rat aorta

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Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA2/isoprostane production

Cited by 12 publications

References 55 publications

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Developmental effect of antenatal exposure to betamethasone on renal angiotensin II activity in the young adult sheep

Cellular mediators of renal vascular dysfunction in hypertension

Selective and potent inhibitory effect of docosahexaenoic acid (DHA) on U46619-induced contraction in rat aorta

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Short-term ANG II produces renal vasoconstriction independent of TP receptor activation and TxA₂/isoprostane production