Acute Blockade of PDGF Receptors Decreases Arterial Blood Pressure and Renal Vascular Resistance in Cyp1a1‐Ren2 Transgenic Rats with Angiotensin II‐Dependent Malignant Hypertension

Abstract

Previous studies have demonstrated that chronic blockade of PDGF receptors prevents the decreases in renal hemodynamic function and renal injury that occur in Cyp1a1‐Ren2 transgenic rats with angiotensin (ANG) II‐dependent malignant hypertension. The present study was performed to determine the effects of acute administration of the PDGF receptor blocker, imatinib mesylate, on mean arterial blood pressure (MAP) and renal hemodynamics during the development of ANG II‐dependent malignant hypertension. Male Cyp1a1‐Ren2 transgenic rats (n=5) were induced to develop malignant hypertension by dietary administration of indole‐3‐carbinol (0.3% wt/wt) for 7 days. Mean arterial pressure (MAP) and renal hemodynamics were measured in pentobarbital‐anesthetized male Cyp1a1‐Ren2 rats during control conditions and following a single intravenous bolus injection of imatinib mesylate (0.2 mg/kg). Imatinib administration decreased MAP (165±5 to 135±9 mmHg, P<0.05) but did not alter either renal plasma flow (2.51±0.11 vs. 2.95±0.21 ml/min.g, NS) or glomerular filtration rate (0.85±0.04 vs. 0.97±0.10 ml/min.g, NS). However, imatinib administration decreased renal vascular resistance in the hypertensive rats (32.3±1.01 to 24.6±1.7 mmHg/ml/min/g, P<0.05). The present findings demonstrate that acute blockade of PDGF receptors elicits decreases in MAP and renal vascular resistance in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension. Thus, the data indicate that activation of PDGF receptors plays an important role in maintaining the elevated MAP and RVR that occurs in ANG II‐dependent malignant hypertension.