A Combination of Hypercholesterolemia and Hypertension Augments an Impairment in Intra-Renal Perfusion Responses
The kidney is a target organ for cardiovascular risk factors, such as atherosclerosis and hypertension (HT), and is particularly susceptible to their combination. Even at an early stage, hypercholesterolemia (HC) and HT are individually associated with impaired renal perfusion responses to challenge with vasodilators. However, the effect of combined HC and HT on renal perfusion remains uncertain. To examine this, regional renal perfusion response to the renal vasodilator acetylcholine (Ach) was quantified in 4 groups of pigs, using electron beam CT, after 12 weeks of either normal (n=6), HC diet (n=6), HT (unilateral renal artery stenosis, n=5), or combined HC and HT (HC+HT, n=6). The HC and HC+HT groups had increased cholesterol levels vs. normal and HT (430±82 and 351±52 vs. 71±6 and 83±4 mg/dl, ANOVA p<0.05, respectively). Mean arterial pressure was significantly elevated in HT and HC+HT vs. normal and HC (132±6 and 127±13 vs. 88±5 and 92±6 mmHg, p<0.05, respectively). The combination of HC and HT was associated with a greater impairment in cortical and papillary perfusion responses than HC or HT alone (Table). Medullary perfusion response was not significantly different among the four groups (Table). These results demonstrate that concurrent HC and HT have a greater detrimental effect on renal perfusion responses than HC or HT alone, and that this effect is regionally heterogeneous. These effects may potentially lead to enhanced renal functional impairment and may play a role in the progression of renal damage in HT and atherosclerosis.