Role of bradykinin B2 receptors in the developmental changes of renal hemodynamics in the neonatal rat

Am J Physiol. 1995 Dec;269(6 Pt 2):F786-92. doi: 10.1152/ajprenal.1995.269.6.F786.

Abstract

The present study was performed to evaluate the role of bradykinin, acting via B2 receptors, in the developmental rise in renal blood flow (RBF) and glomerular filtration rate (GFR) in the rat. Newborn rats were chronically treated from birth with the kinin B2 receptor antagonist HOE-140 (600 micrograms/kg sc, every 12 h, n = 9) or 0.9% saline (n = 7). Weanling rats (mean age 23 days) were anesthetized with pentobarbital sodium (50 mg/kg ip) for measurements of mean arterial pressure (MAP), GFR, and renal plasma flow estimated from p-aminohippurate (PAH) clearance (ERPF). Outer cortical RBF (OCBF) was measured by laser-Doppler flowmetry. Baseline MAP was similar in HOE-140- and saline-treated rats (96 +/- 4 vs. 97 +/- 4 mmHg). Also, baseline GFR (0.65 +/- 0.05 vs. 0.52 +/- 0.08 ml.min-1.g-1) and ERPF (1.6 +/- 0.2 vs. 1.3 +/- 0.1 ml.min-1.g-1) were not different in HOE-140- and saline-treated rats, respectively. Intravenous infusion of 200 ng bradykinin did not change MAP or OCBF in HOE-140 rats but decreased MAP (-29 +/- 3%, P < 0.05) and OCBF (-20 +/- 2%, P < 0.05) in controls. Intravenous infusion of 25 ng angiotensin II increased MAP equally in both groups (-32 +/- 4%) and caused a similar reduction in OCBF (-37 +/- 14 vs. -46 +/- 5%). The angiotensin type 1 (AT1) receptor antagonist losartan (10 mg/kg iv) decreased MAP equally in both groups (-22 +/- 2%). However, AT1 blockade increased ERPF to 3.1 +/- 0.8 ml.min-1.g-1 (P < 0.05 vs. baseline) in saline but not in HOE-140 rats (1.9 +/- 0.4 ml.min-1.g-1). Kidney renin mRNA and angiotensin II contents were not different in HOE-140 vs. saline groups. The present findings indicate that bradykinin is not a primary mediator of the maturational rise in RBF or GFR in the rat. However, the data suggest that under control conditions, angiotensin II, acting via AT1 receptors, counteracts the renal vasodilatory effects of endogenous bradykinin in the developing kidney.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II / metabolism
  • Angiotensin II / pharmacology
  • Animals
  • Animals, Newborn
  • Blood Pressure / drug effects
  • Bradykinin / analogs & derivatives
  • Bradykinin / pharmacology
  • Bradykinin Receptor Antagonists
  • Glomerular Filtration Rate / drug effects
  • Hemodynamics
  • Kidney / growth & development
  • Kidney / metabolism
  • Kidney Cortex / blood supply
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Bradykinin / physiology*
  • Renal Circulation*
  • Renin / genetics
  • Sodium Chloride / pharmacology
  • p-Aminohippuric Acid / pharmacokinetics

Substances

  • Bradykinin Receptor Antagonists
  • RNA, Messenger
  • Receptors, Bradykinin
  • Angiotensin II
  • Sodium Chloride
  • icatibant
  • Renin
  • Bradykinin
  • p-Aminohippuric Acid