Combination of hypercholesterolemia and hypertension augments renal function abnormalities

Hypercholesterolemia and hypertension are both risk factors for end-stage r enal disease. This study was designed to examine whether their coexistence augmented impairment in renal function and redox status. Regional renal hem odynamics and function in response to vasoactive challenges with acetylchol ine or sodium nitroprusside were quantified by using electron-beam computed tomography in pigs after 12 weeks of either a normal (n=10) or hypercholes terolemic (n=10) diet, renovascular hypertension (n=7), or combined hyperch olesterolemia+hypertension (n=6). The hypercholesterolemic and hypercholest erolemic+hypertensive groups had significantly increased serum cholesterol levels, whereas in the hypertensive and hypercholesterolemic+hypertensive g roups, mean arterial pressure was significantly elevated compared with the group fed a normal diet. Basal regional renal perfusion and glomerular filt ration rates were similar among the groups. In response to acetylcholine, c ortical perfusion increased in normal animals (15.6+/-4.7%, P=0.002) but no t in hypercholesterolemic or hypertensive animals (8.0+/-7.4% and 8.2+/-5.9 %, respectively: P>0.05). Moreover, in the hypercholesterolemic+hypertensiv e group, cortical perfusion response was further attenuated (2.5+/-4.8%, P= 0.02) and significantly different from the group fed a normal diet (P<0.05) , The response to sodium nitroprusside followed a similar pattern, and the impairment was augmented in the hypercholesterolemic+hypertensive group. Th e functional abnormalities in hypercholesterolemia or hypertension were ass ociated with a decrease in systemic and/or renal tissue levels of oxygen ra dical scavengers that was again accentuated in hypercholesterolemia+hyperte nsion. These results demonstrate that concurrent hypercholesterolemia and h ypertension have a greater detrimental effect on renal perfusion responses compared with hypercholesterolemia or hypertension alone, associated with a marked pro-oxidant shift in redox status. These effects may potentially au gment renal functional impairment and play a rule in the initiation and pro gression of renal injury in hypertension and atherosclerosis.