Abstract Body: Background: Anecdotal reports showed a decrease in blood pressure (BP) values in subjects assuming macrolide antibiotics when co-administered with calcium channel blockers. Recently, in the MAPA study, in patients with primary hypertension given a single dose of macrolide a decrease in BP was observed. However, whether macrolides induce per se vasorelaxation remains unknown.
Aim: To investigate if macrolides induce vasorelaxation and to identify the underlying mechanisms.
Methods: The effects of 3 macrolides (roxithromycin, azithromycin, clarithromycin) were investigated in a wire myograph in aortas isolated from C57BL/6J mice, following standard protocols. Relaxation/contraction was evaluated in phenylephrine pre-contracted aorta segments exposed to different macrolide concentrations [10^-10 M to 10^-5 M]. Longer-term effects of azithromycin (50 mg/Kg/d intraperitoneally for 14 days) were investigated in vivo in a mouse model of Ang II-induced hypertension. BP was measured with the tail-cuff method; functional and structural/mechanical properties of the aorta and mesenteric arteries were evaluated with wire or pressure myograph, as appropriate.
Results: After exposure to macrolides, phenylephrine pre-contracted mice aorta segments showed relaxation (maximum effect: -15-20% vs DMSO). The vasodilating effect was abolished by the removal of the endothelium, and was blunted by L-NAME. In the vivo studies treatment with azithromycin lowered BP values and prevented Ang II-induced endothelial dysfunction.
Conclusions: Macrolides exert a vasodilatory action that involves endothelium-dependent NO release. In a model of Ang II-mediated hypertension, azithromycin exerted a BP-lowering effect.