Endothelium-derived nitric oxide modulates vascular action of aldosterone in renal arteriole

Shuji Arima, Kentaro Kohagura, Hong Lan Xu, Akira Sugawara, Akira Uruno, Fumitoshi Satoh, Kazuhisa Takeuchi, Sadayoshi Ito

Research output: Contribution to journalArticlepeer-review

81 Citations (Scopus)

Abstract

We have recently demonstrated that aldosterone causes nongenomic vasoconstriction by activating phospholipase C (PLC) in the preglomerular afferent arteriole (Af-Art). In the present study, we tested the hypothesis that endothelium modulates this vasoconstrictor action by releasing nitric oxide (NO). In addition, to study the post-PLC mechanism, we examined possible contributions of phosphoinositol hydrolysis products. Rabbit Af-Arts were microperfused at 60 mm Hg in vitro, and increasing doses of aldosterone (1010 to 108 mol/L) were added to the bath and lumen. Aldosterone caused dose-dependent vasoconstriction (within 10 minutes); significant (P <0.01) constriction was observed from 5X109 mol/L, and at 108 mol/L, intraluminal diameter decreased by 29%3% (n=9). Disrupting the endothelium augmented vasoconstriction; significant constriction was observed from 1010 mol/L, and at 108 mol/L, the diameter decreased by 38%2% (n=6). NO synthesis inhibition reproduced this augmentation (n=7). Pretreatment with chelerythrine (106 mol/L), a protein kinase C (PKC) inhibitor, slightly attenuated the constriction; aldosterone at 108 mol/L now decreased the diameter by 18%3% (n=7). However, in Af-Arts treated with thapsigargin (106 mol/L) or dantrolene (3X105 mol/L), which blocks inositol 1,4,5-triphosphate (IP3)-induced intracellular calcium release, aldosterone at 108 mol/L decreased the diameter by only 9%1% (n=6) or 9%2% (n=5), respectively. These results demonstrate that in the Af-Art endothelium-derived NO modulates vasoconstrictor actions of aldosterone that are mediated by the activation of both IP3 and PKC pathways. Such vasoconstrictor actions of aldosterone may contribute to the development or aggravation of hypertension by elevating renal vascular resistance in cardiovascular diseases associated with endothelium dysfunction.

Original languageEnglish
Pages (from-to)352-357
Number of pages6
JournalHypertension
Volume43
Issue number2
DOIs
Publication statusPublished - 2004 Feb

Keywords

  • Aldosterone
  • Arterioles
  • Endothelium
  • Inositol
  • Nitric oxide
  • Phospholipases
  • Protein kinases

ASJC Scopus subject areas

  • Internal Medicine

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