Attenuation of hypertension-mediated glomerulosclerosis in conjunction with increased angiotensin (1-7)

Ther Adv Cardiovasc Dis. 2011 Dec;5(6):297-304. doi: 10.1177/1753944711429343. Epub 2011 Nov 16.

Abstract

Background: Controversy exists as to whether angiotensin (1-7) (Ang (1-7)) acts as a protective hormone against renal injury.

Methods: We compared the degree of improvement of hypertensive nephropathy following 8 weeks' treatment with either the angiotensin II receptor type 1 antagonist olmesartan medoxomil or the cardioselective beta blocker atenolol in 8-week-old spontaneously hypertensive rats (SHRs).

Results: Both treatment regimens reduced mean blood pressure in a similar fashion, while bradycardia was present only in atenolol-treated SHRs. The heart weight:body weight ratio fell more in SHRs medicated with olmesartan versus those receiving atenolol. These changes were associated with increases in plasma Ang II in SHRs given the angiotensin II receptor blocker. At the end of treatment, plasma Ang (1-7) was higher in the olmesartan than atenolol or vehicle groups. The glomerular sclerosis (GS) index was lowered by olmesartan and atenolol compared with the vehicle group. While both olmesartan and atenolol attenuated renal perivascular collagen deposition (PVCD), the greatest effect was observed in SHRs receiving olmesartan. Elevations in plasma Ang (1-7) correlated negatively with reductions in GS or PVCD index, respectively.

Conclusions: While control of blood pressure remains a critical factor in the prevention of hypertensive nephropathy, Ang (1-7) may play a substantial role in preventing the structural changes in glomerulus through its effect on regulations of blood pressure and renal function.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-1 Receptor Antagonists / pharmacology*
  • Adrenergic beta-1 Receptor Antagonists / therapeutic use
  • Angiotensin I / blood
  • Angiotensin I / physiology*
  • Angiotensin II Type 1 Receptor Blockers / pharmacology*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use
  • Animals
  • Atenolol / pharmacology*
  • Atenolol / therapeutic use
  • Blood Pressure / drug effects*
  • Hemodynamics / drug effects
  • Hypertension / complications
  • Imidazoles / pharmacology*
  • Imidazoles / therapeutic use
  • Kidney Diseases / complications
  • Kidney Glomerulus / drug effects
  • Kidney Glomerulus / pathology
  • Male
  • Olmesartan Medoxomil
  • Peptide Fragments / blood
  • Peptide Fragments / physiology*
  • Rats
  • Rats, Inbred SHR
  • Sclerosis
  • Tetrazoles / pharmacology*
  • Tetrazoles / therapeutic use

Substances

  • Adrenergic beta-1 Receptor Antagonists
  • Angiotensin II Type 1 Receptor Blockers
  • Imidazoles
  • Peptide Fragments
  • Tetrazoles
  • Atenolol
  • Olmesartan Medoxomil
  • Angiotensin I
  • angiotensin I (1-7)