Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II

Tsuneo Takenaka, Hiromichi Suzuki, Keiji Fujiwara, Yoshihiko Kanno, Yoichi Ohno, Koichi Hayashi, Takahiko Nagahama, Takao Saruta

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49 Citations (Scopus)

Abstract

To assess cellular mechanisms mediating afferent (AA) and efferent arteriolar (EA) constriction by angiotensin II (AngII), experiments were performed using isolated perfused hydronephrotic kidneys. In the first series of studies, AngII (0.3 nM) constricted AAs and EAs by 29±3 (n = 8, P < 0.01) and 27±3% (n = 8, P < 0.01), respectively. Subsequent addition of nifedipine restored AA but not EA diameter. Manganese (8 mM) reversed EA constriction by 65±9% (P < 0.01). In the second group, the addition of N-ethylmaleimide (10 μM), a Gi/Go protein antagonist, abolished AngII-induced EA (n = 6) but not AA constriction (n = 6). In the third series of experiments, treatment with 2-nitro-4-carboxyphenyl-N,N-diphenyl-carbamate (200 μM), a phospholipase C inhibitor, blocked both AA and EA constriction by AngII (n = 6 for each). In the fourth group, thapsigargin (1 μM) prevented AngII-induced AA constriction (n = 8) and attenuated EA constriction (8±2% decrease in EA diameter at 0.3 nM AngII, n = 8, P < 0.05). Subsequent addition of manganese (8 mM) reversed EA constriction. Our data provide evidence that in AAs, AngII stimulates phospholipase C with subsequent calcium mobilization that is required to activate voltage-dependent calcium channels. Our results suggest that AngII constricts EAs by activating phospholipase C via the Gi protein family, thereby eliciting both calcium mobilization and calcium entry.

Original languageEnglish
Pages (from-to)2107-2114
Number of pages8
JournalJournal of Clinical Investigation
Volume100
Issue number8
DOIs
Publication statusPublished - 1997 Oct 15

Keywords

  • Calcium entry
  • Calcium mobilization
  • GTP-binding protein
  • Glomerular arteriole
  • Phospholipase C

ASJC Scopus subject areas

  • Medicine(all)

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    Takenaka, T., Suzuki, H., Fujiwara, K., Kanno, Y., Ohno, Y., Hayashi, K., Nagahama, T., & Saruta, T. (1997). Cellular mechanisms mediating rat renal microvascular constriction by angiotensin II. Journal of Clinical Investigation, 100(8), 2107-2114. https://doi.org/10.1172/JCI119745