Abstract
I examined the rapid vasomotor action of HDL on excised, precontracted porcine coronary artery strips. HDL (500 μg protein/ml) isolated from human plasma were applied to strips precontracted with 6μM prostaglandin (PG) F2α. Contractions induced by PGF2α spontaneously declined by 4.0±0.4% (n=22) and 9.8±1.3% (n =5) at 30 and 50 min, respectively. When HDL was applied at 30 min, relaxation of the coronary strips at 50 min was significantly enhanced to 17.4±1.2% (n=7). Decreased strip tension elicited by HDL was significantly larger than the control throughout the 20 min test period. The role of endothelium in the HDL-induced vasomotor response was determined by examining the effect of HDL on coronary artery strips denuded of endothelium. The total decline in tension over the entire course of the 50 min test period was 10.2±2.7% (n=4) in the absence of HDL and 10.8±2.6% (n=4) in the presence of HDL. Thus, HDL failed to affect PGF2α - induced contraction in the endothelium-denuded arterial strips. Addition of NG - monomethyl- L- arginine (L-NMMA, 300 μM) 10 min before PGF2α caused a small immediate increase in resting tension (5.8±0.7%) and increased the peak amplitudes of PGF2α-induced contractions by 33.8±7.8% (n=10). L-NMMA, however, did not affect either the time-dependent decline in PGF2α- induced tension or HDL-induced relaxation. Strip tension declined by 5.6±0.8% (n=10) at 30 min, and total relaxation during the 50 min test period was 10.0±1.2% (n=6) in the absence of HDL and 17.6±2.5% (n=4) in the presence of HDL. The extent of relaxation was similar to that without L-NMMA. To examine the contribution of endothelium-derived prostanoids to HDL-induced relaxation, coronary artery strips were pretreated with indomethacin (10 μ M; IM) for 10 min prior to the addition of PGF2α. IM caused a slow decline in the resting tension (5.6±1.1%) and decreased peak amplitudes of PGF2α-induced contraction (30.5±6.1%; n=10). The rate of increase in strip tension was also markedly slowed. The spontaneous relaxation over 50 min in the presence of IM was 6.2±2.7% (n=4). When HDL was applied to IM-treated, PGF2α-precontracted strips, HDL no longer elicited relaxation, but instead provoked gradual increases in tension (10.5±1.9%; n= 6) which became significant within 10 min. In conclusion, native human HDL elicited endothelium-dependent vasorelaxation in porcine coronary artery strips precontracted with PGF2α. This relaxation was abolished when cyclooxygenase was inhibited by IM. Thus, HDL may affect vasomotor tone by stabilizing endothelium-derived PGI2.
