Correction of disturbances in neuroregulatory systems at early stages of atherogenesis with verapamil

Abstract

The effect of verapamil on morphofunctional state of the hypothalamo-pituitary neurosecretory system, adrenergic innervation of microvessels, and microcirculation in the early stages of atherogenesis was studied. Correction of functional aberrations of the neuroregulatory systems and microcirculatory disturbances with verapamil was accompanied by restoration of lipid homeostasis and less pronounced atherosclerotic alterations in major arteries. Key Words: verapamil; hypothalamo-pituitary neurosecretory system; adrenergic innervation of microvessels; atherosclerosisThe hypothalamo-pituitary neurosecretory system (HPNS) and peripheral subdivision of the sympathoadrenal system (SAS), which produce bioactive substances with vasoactive and lipid mobilizing effect (vasopressin, norepinephrine), play an important role in the mechanisms of atherogenesis. There is a correlation between functional state of these systems, microcirculatory disturbances, and the degree of atherosclerotic process in major arteries during hyperlipemia [2,5,8].In view of the priming role of microcirculatory disturbances in the development of polyorgan pathology during hyperlipidemia [4], the search for means of correction of functional disturbances in HPNS and SAS is actual. It was established that some calcium channel blockers affect lipid metabolism and modulate activity of the antioxidant system and SAS [7,10,11]. Calcium blocker verapamil is an active neuroprotector, which protects, in particularly, the neurosecretory pituitary cells [6].Our aim was to study the effect of verapamil on morphofunctional state of the regulatory systems at the early stages of atherogenesis. MATERIALS AND METHODSExperiments were performed on 30 male Chinchilla rabbits weighing 2.5-3.0 kg. Group 1 rabbits (intact controls) were maintained on a standard diet. Group 2 rabbits were given 0.3 g/kg cholesterol during 2 months, which modeled atherogenic diet (ATD) according to N. N. Anichkov. Group 3 rabbits were intramuscularly injected with verapamil (phynoptin, Orion) in a dose of 0.5 mg/kg for 10 days during the 2nd month of the diet. We previously observed marked accumulation of LDL, pronounced changes in HPNS, peripheral subdivision of SAS (adrenergic innervation of microvessels), and microcirculatory vascular bed, and initial lipidosis of the aortal intima after one month of ATD [3,5]. Plasma level of total HDL and LDL fractions were determined. The degree of atherosclerotic process was assessed by the index of atherosclerotic damage (lAD) to the aorta [13]. The hypothalamic supraoptic (SO) nuclei and neurohypophysis were studied on serial brain slices by the methods of Gomori--Maiorova, Nissl, and Milenkov. The functional state of HPNS was assessed as described elsewhere [9] by the content of Gomori-positive substance in neurosecretory cells, hypothalamo-pituitary tract, and posterior pituitary. The percentage of "bright" and