BLOOD LIPOPROTEIN SPECTRUM AND THE LEVEL OF VASOACTIVE ENDOTHELIAL FACTORS IN CHILDREN WITH ARTERIAL HYPOTENSION

The article presents the data on the characteristic features of lipoprotein metabolism and the level of vasoactive endothelial factors in children with primary and symptomatic arterial hypotension. Dyslipidemia in the first group of patients is characterized by an increase in low-density lipoprotein cholesterol, apolipoprotein B100, the atherogenicity coefficient, the ApoLP atherogenicity index, a high concentration of nitric oxide in case of low levels of high-density lipoprotein cholesterol and ApoLP A1. In children with chronic gastroduodenal pathology and symptomatic arterial hypotension, the above disorders of lipoprotein metabolism and endothelial function are accompanied by an increased content of total cholesterol and bradykinin. These data suggest that in children with primary and symptomatic arterial hypotension, conditions for the formation of the initial atherosclerotic process are created due to the predominance of the pro-atherogenic Apo B100 transporter protein over the anti-atherogenic Apo A1, as well as due to a significant increase in nitric oxide and endothelial dysfunction.

Relaxant and antiadrenergic effects of ranolazine in human saphenous vein

OBJECTIVES Ranolazine improves vascular function in animal models. We evaluate the effects of ranolazine on vascular function and adrenergic response in human saphenous vein. METHODS Rings from 53 patients undergoing coronary artery bypass grafting were mounted in organ baths. Concentration–response curves to ranolazine were constructed in rings precontracted with phenylephrine, endothelin-1, vasopressin, KCl and the thromboxane A2 analogue U-46619. In rings precontracted with phenylephrine, relaxation to ranolazine was tested in the absence and presence of endothelial factors inhibitors, K+ channel blockers and verapamil. The effects of ranolazine on frequency–response and concentration–response curves to phenylephrine were performed in the absence and presence of endothelial factors inhibitors and K+ channel blockers. Endothelial nitric oxide synthase, α1 adrenergic receptor and large conductance Ca2+-activated K+ channel protein expressions were measured by Western blotting. RESULTS Ranolazine (10−9–10−4 M) produced a concentration-dependent relaxation only in rings precontracted with phenylephrine that was reduced by endothelial denudation, NG-nitro-l-arginine methyl ester (10−4 M), charybdotoxin (10−7 M) and verapamil (10−6 M). Ranolazine diminished adrenergic contractions induced by electrical field stimulation (2–4 Hz) and phenylephrine (10−9–10−5 M) that were prevented by tetraethylammonium (10−3 M) and charybdotoxin (10−7 M). Ranolazine significantly decreased α1 adrenergic receptor and increased large conductance Ca2+-activated K+ channel protein expression in the saphenous vein. CONCLUSIONS Ranolazine diminishes the adrenergic vasoconstriction, acting as α1 antagonist, and by increasing large conductance Ca2+-activated K+ channel involvement. The relaxant effects of ranolazine are partially mediated by endothelial nitric oxide, large conductance Ca2+-activated K+ channels and the blockade of voltage-dependent Ca2+ channels.