title: Nongenomic vascular action of aldosterone in the glomerular microcirculation.
abstract: Aldosterone (Aldo) accelerates hypertension, proteinuria, and glomerulosclerosis in animal models of malignant hypertension or chronic renal failure. Aldo may exert these deleterious renal effects by elevating renal vascular resistance and glomerular capillary pressure. To test this possibility, directly examined were the action of Aldo on the afferent (Af) and efferent (Ef) arterioles (Arts). Examined were the effect of Aldo added to both the bath and lumen on the intraluminal diameter (measured at the most responsive point) of rabbits. Aldo caused dose-dependent constriction in both arterioles with a higher sensitivity in Ef-Arts. Vasoconstrictor action of Aldo was not affected by a mineralocorticoid receptor antagonist spironolactone and was reproduced by membrane-impermeable albumin-conjugated Aldo, suggesting that the vasoconstrictor actions are nongenomic. Pretreatment with neomycin (a specific inhibitor of phospholipase C) abolished the vasoconstrictor action of Aldo in both arterioles. In addition, the vasoconstrictor action of Aldo on Af-Arts was inhibited by both nifedipine and efonidipine, whereas that on Ef-Arts was inhibited by efonidipine but not nifedipine. The results demonstrate that Aldo causes nongenomic vasoconstriction by activating phospholipase C with a subsequent calcium mobilization thorough L- or T-type voltage-dependent calcium channels in Af- or Ef-Arts, respectively. These vasoconstrictor actions on the glomerular microcirculation may play an important role in the pathophysiology and progression of renal diseases by elevating renal vascular resistance and glomerular capillary pressure.
authors.affiliation: Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University School of Medicine, Sendai, 980-8574, Japan. shuarima@mail.cc.tohoku.ac.jp
authors.forename: Shuji
authors.initials: S
authors.lastname: Arima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kohagura
authors.forename: Hong-Lan
authors.initials: HL
authors.lastname: Xu
authors.forename: Akira
authors.initials: A
authors.lastname: Sugawara
authors.forename: Takaaki
authors.initials: T
authors.lastname: Abe
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Satoh
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Sadayoshi
authors.initials: S
authors.lastname: Ito
mesh_terms: D000450:Aldosterone / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000503:physiopathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000503:physiopathology; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009355:Neomycin / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011817:Rabbits; D013148:Spironolactone / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D000451:Mineralocorticoid Receptor Antagonists; D011500:Protein Synthesis Inhibitors; D003609:Dactinomycin; D013148:Spironolactone; D000450:Aldosterone; D003513:Cycloheximide; D009355:Neomycin