Abstract 3541: Deficiency of Lrp1 in Smooth Muscle Cells Decreases Diastolic Blood Pressure and Abolishes the Pressor Response to Angiotensin Ii: Novel Role in Blood Pressure Regulation
The LDL receptor-related protein-1 (LRP1) is expressed abundantly in vascular tissues, and hypercholesterolemic mice with defective LRP1 expression in smooth muscle cells (smLRP1−/−) exhibit aberrant thickening of the aortic medial layer with accelerated atherosclerosis and abdominal aortic aneurysm formation. However, the role of LRP1 in blood pressure regulation has not been examined. We measured heart rate and arterial blood pressure in chow-fed smLRP1−/− and wild-type littermates via intra-arterial probes. Measurements were taken under baseline conditions and during infusion of angiotensin II (1000 ng/kg/min) by osmotic minipump for 7 days (Table⇓). Mean heart rate was higher in smLRP1−/− mice as compared with wild-type mice. Baseline mean arterial blood pressure (MBP) was marginally reduced, while diastolic blood pressure (DBP) was significantly reduced, in smLRP1−/− mice as compared with wild-type mice. In contrast, systolic blood pressure (SBP) did not differ between the two groups of mice. Angiotensin II infusion significantly increased MBP, SBP and DBP in wild-type mice, but had no effect on these parameters in smLRP1−/− mice. These novel results indicate that defective LRP1 expression in smooth muscle cells leads to reduction in diastolic blood pressure and abolishes the pressor response to angiotensin II. We conclude that LRP1 in smooth muscle cells plays a role in blood pressure regulation, most likely by modulating arteriolar function.