Brief losartan treatment in young spontaneously hypertensive rats abates long-term blood pressure elevation by effects on renal vascular structure.

摘要

OBJECTIVE : We studied the importance of regional vascular structural changes for the long-term antihypertensive effect of brief angiotensin II receptor blockade with losartan in young spontaneously hypertensive rats (SHRs). DESIGN/METHODS : SHRs were treated from 3 to 8 weeks of age with losartan (SHRLos, 30 mg/kg per day in drinking water) or vehicle (SHRCon). Mean arterial blood pressure (MAP) was measured using a telemetric technique from 12 to 25 weeks of age. Indices of vascular structure in the renal and hindquarter limb (HQ) were assessed using a haemodynamic perfusion technique at 13-15 weeks of age. RESULTS : MAP in SHRLos was reduced by 20-30 mmHg throughout the study (P < 0.001) and left ventricular weights were reduced (P < 0.05). The slope of the pressure/flow relationship was significantly changed (P < 0.001) in both kidneys and HQ vascular beds, suggesting greater average lumen dimensions in SHRLos. Pressure-glomerular filtration rate (GFR) curves of SHRLos kidneys were shifted to the left (P < 0.001), suggesting that the reduction in renal vascular resistance was predominantly preglomerular. The changes in structural indices of the heart and HQ closely followed the reduction in MAP. However, resistance at maximal dilatation in SHRLos kidneys was changed out of proportion to the lowering in MAP (P < 0.01). CONCLUSIONS : Brief losartan treatment in young SHRs reduces long-term MAP. The reduced MAP is associated with higher average renal and skeletal muscle vascular dimensions at maximal dilatation, predominantly in the pre-capillary vasculature. The reduction in vascular resistance of the kidney appears to be out of proportion to the reduction in MAP and it may be speculated that this is of primary importance in the long-term hypotensive effect of brief angiotensin II antagonism in SHRs.