Localization of endothelin-like immunoreactivity in rat kidneys

Wilkes, Barry M.; Susin, Myron; Mento, P. F.; Macica, Carolyn M.; Girardi, Erika; Boss, Eleanor; Nord, Edward P.

doi:10.1152/ajprenal.1991.260.6.f913

Cited by 47 publications

(40 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In situ hybridization of renal cortex revealed no ET-1 mRNA in any mice (floxed ET-1, AQP2-Cre, or CD ET-1 KO). The lack of detectable renal cortical ET-1 is in agreement with other studies using in situ hybridization, immunostaining, or RT-PCR of immunodissected CCD (6,8,38,39). To confirm that recombination had occurred in CCDs, the ducts were microdissected and DNA PCR amplified using the primers used for genotyping.…”

Section: Resultssupporting

confidence: 88%

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

Ahn¹,

Ge²,

Stricklett³

et al. 2004

J. Clin. Invest.

228

158

View full text Add to dashboard Cite

In vitro studies suggest that collecting duct-derived (CD-derived) endothelin-1 (ET-1) can regulate renal Na reabsorption; however, the physiologic role of CD-derived ET-1 is unknown. Consequently, the physiologic effect of selective disruption of the ET-1 gene in the CD of mice was determined. Mice heterozygous for aquaporin2 promoter Cre recombinase and homozygous for loxP-flanked exon 2 of the ET-1 gene (called CD-specific KO of ET-1 [CD ET-1 KO] mice) were generated. These animals had no CD ET-1 mRNA and had reduced urinary ET-1 excretion. CD ET-1 KO mice on a normal Na diet were hypertensive, while body weight, Na excretion, urinary aldosterone excretion, and plasma renin activity were unchanged. CD ET-1 KO mice on a high-Na diet had worsened hypertension, reduced urinary Na excretion, and excessive weight gain, but showed no differences between aldosterone excretion and plasma renin activity. Amiloride or furosemide reduced BP in CD ET-1 KO mice on a normal or high-Na diet and prevented excessive Na retention in salt-loaded CD ET-1 KO mice. These studies indicate that CD-derived ET-1 is an important physiologic regulator of renal Na excretion and systemic BP. IntroductionEndothelin-1 (ET-1) was initially described as a potent endothelial cell-derived vasoconstrictor (1); however, the peptide is now known to be produced by many cell types and to elicit multiple biologic effects (2). The kidney is likely an important target; ET-1 causes renal vasoconstriction, mesangial cell contraction, glomerular cell proliferation, ECM accumulation, and alterations in nephron fluid and electrolyte transport (2). While many renal cell types synthesize and bind ET-1, the collecting duct (CD) is of particular importance: The renal inner medulla contains the highest concentration of ET-1 in the body (3), and the inner medullary CD (IMCD) is the predominant renal site of ET-1 production (4-8) and receptor expression (9-11).In vitro studies suggest that ET-1 inhibits Na and water reabsorption in the cortical CD (CCD) and IMCD and that this occurs through activation of the ET B receptor (ETRB). ET-1 inhibits vasopressin-stimulated (AVP-stimulated) water flux in isolated CCD (9, 12) and reduces AVP-stimulated cyclic AMP accumulation (13-15) and osmotic water permeability (16, 17) in isolated IMCDs. ET-1 also inhibits mineralocorticoid and AVP-stimulated Na and Cl reabsorption in isolated CCDs (12,18,19) and decreases Na/K-ATPase activity in suspensions of IMCDs (20). Despite these data, demonstrating such an ET-1 effect in vivo and clarifying how CD-derived ET-1 physiologically regulates Na and water transport has been problematic. This difficulty stems, in part, from

show abstract

Section: Resultssupporting

confidence: 88%

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

Ahn¹,

Ge²,

Stricklett³

et al. 2004

J. Clin. Invest.

228

158

View full text Add to dashboard Cite

show abstract

“…The latter is separated from distal tubules in vivo by only a very narrow interstitial space (45), permitting paracrine or autocrine communication among cell types. In addition, microdissected cortical collecting tubules contain ET-1 mRNA (43,46), and ET-1 is on the endothelial surfaces of peritubular capillaries (44). The present studies show that dietary acid increases RIF ET-1 addition and suggest that the added ET-1 subsequently increases distal tubule acidification.…”

Section: Discussionsupporting

confidence: 53%

“…Furthermore, rat cortical collecting tubules contain mRNA for the B-type endothelin receptor (43), which the present studies suggest mediates the described actions of endogenous endothelins. Endothelins in the RIF might derive from collecting tubule epithelium (5) or endothelium of the renal microvasculature (6,44). The latter is separated from distal tubules in vivo by only a very narrow interstitial space (45), permitting paracrine or autocrine communication among cell types.…”

Section: Discussionmentioning

confidence: 99%

Endogenous endothelins mediate increased distal tubule acidification induced by dietary acid in rats.

Wesson¹

1997

J. Clin. Invest.

105

View full text Add to dashboard Cite

show abstract

“…13 - 15 In addition, receptors for both peptides have been identified in the glomeruli, vasa recta, and medulla. 22 Localized stimulation of renal Ang II formation by ET-1 therefore could contribute to the observed hypertension, which would be reversed by an action of captopril on renal ACE. In support, one recent investigation performed in anesthetized dogs and rats demonstrated that captopril attenuated ET-1-induced decreases in renal blood flow, urinary sodium excretion, and urine flow, while having little effect on the shortterm pressor response to ET-1.…”

Section: C1 C2 C3 E1 E2 E3 E4 Es E« E7 R1 R2 Rj R4 R5mentioning

confidence: 99%

Captopril prevents chronic hypertension produced by infusion of endothelin-1 in rats.

Mortensen

Fink

1992

Hypertension

View full text Add to dashboard Cite

Endothelin-1 (ET-1), a potent vasoconstrictor peptide synthesized by the vascular smooth muscle endothelium, has been previously shown to produce a sustained, salt-sensitive elevation in mean arterial pressure when chronically infused over a 7-day period into male Sprague-Dawley rats. In addition to other physiological actions, ET-1 has been shown to have potent effects on various renal functions, including renin production. Activation of the renin-angiotensin system, therefore, may contribute to the pressor response induced by ET-1. In this investigation, captopril ([2S]-l-[3-mercapto-2-methylpropionyl]-Lproline), a sulfhydryl-containing angiotensin I converting enzyme inhibitor, was chronically administered to endothelin-infused rats to elucidate the role of the renin-angiotensin system in this animal model of hypertension. Rats were catheterized, housed in metabolic cages, and maintained on a fixed 6.0 meq • day" 1 sodium intake throughout the experiment, with daily measurements taken of mean arterial pressure, heart rate, water intake, urine output, and urinary sodium and potassium excretions. Infusion of ET-1 alone at a rate of 5.0 pmol • kg" 1 • min" 1 for 7 days was associated with a significant and sustained increase in mean arterial pressure; concomitant chronic administration of captopril in another group of rats at a rate of 1.0 mg • kg" 1 • hr~' prevented the ET-1-induced hypertension. In an additional study, however, increases in plasma angiotensin II concentration were not observed in rats administered ET-1 alone at 5.0 pmol • kg" 1 • min~'. These results indicate that endothelin-induced hypertension may involve stimulation of the renin-angiotensin system but not an increase in circulating angiotensin II concentration. (Hypertension 1992;19:676-680) KEY WORDS • endothelin • captopril • renin-angiotensin system • chronic hypertension • rat studies S ince the isolation of the endothelial-produced, vasoactive peptide endothelin in 1988, extensive investigations into its biochemical and physiological nature have been performed. Presently, although the biochemical nature of this family of peptides has been extensively described in the available literature, 1 much of the physiology of the endothelins remains to be elucidated. Likewise, the relevance of circulating or endothelial-derived endothelin in cardiovascular physiology or pathophysiology has not been firmly established. Considerable evidence exists, however, that suggests a possible pathophysiological role for circulating endothelin.2 For example, recent reports implicate the endothelin-1 (ET-1) isoform in several diseases, including cerebral ischemia, 3 myocardial infarction, 4 congestive heart failure, 5 hypertension, 6 and hemangioendothelioma (endothelin-secreting tumor), 7 as these clinical situations were associated with significantly elevated plasma levels of endothelin. Alternatively, because this vasoactive peptide is produced ubiquitously throughout the vascular endothelium 8 and other cardiovascular structures, 9 there is also reason ...

show abstract

Localization of endothelin-like immunoreactivity in rat kidneys

Cited by 47 publications

References 0 publications

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

Collecting duct–specific knockout of endothelin-1 causes hypertension and sodium retention

Endogenous endothelins mediate increased distal tubule acidification induced by dietary acid in rats.

Captopril prevents chronic hypertension produced by infusion of endothelin-1 in rats.

Contact Info

Product

Resources

About