Vasoactive Mediators Affect the Clearance of Lipids from Emulsion Models of Plasma Lipoproteins in Rats

We wished to establish whether the haemodynamic changes accompanying alterations in blood pressure exert a direct effect on clearance of chylomicron-like emulsions. N-Nitro-L-arginine (NOLA) and endothelin-1 were used to increase the blood pressure of normotensive rats, sodium nitroprusside (NP) and calcitonin gene-related peptide (CGRP) were used to decrease the blood pressure of spontaneously hypertensive rats (SHR). The lipid emulsions contained radiolabeled triolein (TO) and cholesteryl oleate (CO) to trace plasma clearances. NP and CGRP enhanced TO clearance in the SHR but slowed the rate of CO clearance. NOLA in normotensive rats clearly slowed the rate of TO removal and also retarded CO clearance, whereas with endothelin-1 TO clearance remained unaffected and CO removal was markedly slowed. The effects on TO clearance are consistent with changes in arteriolar resistance regulating access of emulsion particles to lipoprotein lipase on the endothelial cells of capillaries in muscle and adipose tissue. The changes in CO removal rate are more difficult to interpret because factors determining hepatic blood flow are complex. The results suggest that haemodynamic changes potentially affect circulation times of various lipoprotein species in the plasma, with probable consequences in relation to atherogenesis.