Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries.

Abstract

We studied the effects of hypercholesterolemia on the vascular responses of proximal and distal parts of the rabbit coronary circulation in two consecutive studies. For 12 weeks, New Zealand White rabbits were fed a control diet or a diet with 1% cholesterol dissolved in either 3% coconut oil (study A) or ether (study B). Isolated proximal epicardial and distal intramyocardial coronary arteries from control and hypercholesterolemic rabbits were mounted for isometric tension recording in a double myograph. In study A for hypercholesterolemic rabbits (A=12), the maximal relaxation and sensitivity to acetylcholine (ACh) were significantly decreased in proximal coronary segments contracted with 30 mmol/1 potassium solution compared with segments from control rabbits (it=13). The only change observed in distal coronary segments was a slight decrease in relaxation in response to low ACh concentrations (10~* and 3 x 10~* mol/1). However, in study B for proximal coronary and distal coronary segments from hypercholesterolemic rabbits (n=13), the area under the ACh relaxation curve was increased compared with that of control r abbits (n = 12). Other parameters that were similarly affected in studies A and B include the following: 1) proximal coronary segments from hypercholesterolemic rabbits were more sensitive to sodium nitroprusside (SNP) than were those from control rabbits, but this was not true for distal coronary segments; 2) endothelial removal from arterial segments of control rabbits induced a significant increase in sensitivity and maximal relaxation to SNP of proximal coronary and distal coronary arteries; 3) in segments from hypercholesterolemic rabbits, the absence of endothelium did not alter the response of proximal coronary segments to SNP but did augment the relaxation of distal coronary segments to SNP; 4) the maximal response to 5-hydroxvtrvptamine in proximal coronary arteries from hypercholesterolemic rabbits was increased compared with those from control rabbits, whereas such changes were not observed in distal coronary arteries; and 5) histological examination showed the presence of atheromatous plaques in proximal coronary but not in distal coronary segments from treated animals. In conclusion, the present investigation demonstrates that induced hypercholesterolemia alters both the structure and function of proximal parts of the coronary circulation. In distal coronary arteries of hypercholesterolemic rabbits, the only change observed was an impaired endothelium-dependent cholinergie relaxation, but even this change appeared to be dependent on the manner in which cholesterol was added to the diet, although parallel studies are required to confirm this. (

Heterogeneity of muscarinic receptors in lamb isolated coronary resistance arteries

“…In the present study, pirenzepine acted as a non-competitive antagonist against ACh in the presence of the endothelium and as a competitive antagonist when the endothelium was removed, while both AFDX 116 and pFHHSiD acted as competitive antagonists in arteries both with and without endothelium, although the pKB for pFHHSiD was underestimated in endothelium-intact preparations ( Figure 5). Alosachie & Godfraind (1988) Tschudi et al, 1991;Simonsen et al, 1992).…”

“…In vitro studies of isolated coronary resistance arteries, which excluded the influence of myocardial oxygen consumption and metabolic regulation of coronary blood flow, show the same species differences to cholinergic stimulation as in vivo studies. ACh relaxes preconstricted rat, rabbit and dog coronary resistance arteries (Nyborg, 1990;Angus et al, 1991;Simonsen et al, 1992), while it induces atropinesensitive contraction of small porcine arteries in vitro (Nakayama et al, 1988;Angus et al, 1991;Tschudi et al, 1991). In human small coronary arteries isolated from the atrial appendage, ACh induces contraction, even in arteries with a functional endothelium, assessed by a relaxation to substance P (Angus et al, 1991).…”

Anaphylaxis of small arteries: putative role of nitric oxide and prostanoids

“…Small arteries are attractive because of their great contribution to the regulation of blood pressure. Arteries from different vascular beds show heterogeneous mechanisms of vascular relaxation (23)(24)(25), and for this reason, we investigated arteries from different organs -coronary and mesenteric.…”

Endothelial Function and Mechanical Properties of the Common Carotid Artery in Children on Parenteral Nutrition

“…Diet-induced hypercholesterolemia is the most common model of nondenuding endothelial injury, closely resembling human spontaneous atherosclerosis (13). The relationship between dyslipidemia and vascular endothelium has been well established, not only in adults but also in children (4,14).…”