PDGF receptor antagonism prevents the increase in kidney ANG II levels in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension (1136.1)

Abstract

This study was performed to determine if chronic PDGF receptor blockade prevents the augmentation of intrarenal ANG II levels in Cyp1a1‐Ren2 transgenic rats with ANG II‐dependent malignant hypertension. Male Cyp1a1‐Ren2 rats (n=5/group) were induced to develop malignant hypertension by dietary administration of indole‐3‐carbinol (I3C, 0.3% wt/wt) for 10 days. Systolic blood pressures (SBP) were measured daily by tail‐cuff plethysmography. On day 10 of I3C administration, rats were subjected to conscious decapitation and trunk blood was collected for measurement of plasma renin activity (PRA) and plasma ANG II levels. The kidneys were harvested for determination of total kidney ANG II levels. Dietary I3C resulted in increases in SBP (130±5 to 171±9 mmHg, P<0.05), PRA (64±6 vs. 5±1 ng ANG I/ml/hr, P<0.001), plasma ANG II levels (186±26 vs. 139±10 fmol/ml, P<0.05), and total kidney ANG II content (550±31 vs. 253±24 fmol/g, P<0.001). Chronic imatinib administration (60 mg/kg/day, oral gavage) did not prevent the development of hypertension (187±10 vs. 141±2 mmHg, P<0.001) or the increase in PRA (72±6 vs. 5±1 ng ANG I/ml/hr, P<0.001), but prevented the I3C‐induced augmentation of intrarenal ANG II levels (285±128 vs. 253±24 fmol/g). The present findings indicate that PDGF receptor activation contributes to the increase in the elevations of intrarenal ANG II levels in ANG II‐dependent malignant hypertension.Grant Funding Source: 5P30GM103337