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

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.