Hereditary Hypertriglyceridemic Rat: A New Animal Model of Metabolic Alterations in Hypertension

Abstract

Hereditary hypertriglyceridemic rats (hHTg) were developed as a new genetic model for the study of relationships between blood pressure (BP) and metabolic abnormalities. This strain has been produced by selective inbreeding from Wistar rats according to the rise of plasma triglycerides induced by a high-sucrose diet. Though hHTg rats display hypertriglyceridemia, impaired glucose tolerance, hyperinsulinemia, insulin resistance and increased BP even without nutritional stimuli, high sucrose feeding further aggravates these symptoms. High plasma triglycerides levels in hHTg rats seem to be a consequence of their hyperproduction. Impaired insulin action is responsible for the defective glucoregulation in this strain. The loss of insulin responsiveness might be due to a reduction in the number of glucose transporters. Highly significant relationships among plasma triglycerides, ouabain-resistant Na+ transport and BP were demonstrated in the hHTg rats. Segregating populations (F2 hybrids) should be used for genetic analysis of the primary role of lipid and/or ion transport abnormalities in the pathogenesis of this form of genetic hypertension.

Mapping of genetic loci predisposing to hypertriglyceridaemia in the hereditary hypertriglyceridaemic rat: analysis of genetic association with related traits of the insulin resistance syndrome

“…The hHTg rat strain was selected solely on the basis of a plasma Tg response to a high monosaccharide diet [5]. Thus, the subsequent finding [4] of moderate hypertension in the model, in the context of previous data on the IR syndrome [2], strongly suggested that a common genetic basis could underlie the dyslipidaemia and hypertension. It was therefore quite surprising to observe that neither the chromosome 4 nor the chromosome 8 Tg QTLs had any effect on BP despite the very powerful effects on Tg concentration.…”

“…The derivation of the hHTg strain is described elsewhere [4]. The rats used in this study were from a colony set up at the Institute of Experimental Endocrinology in Bratislava, Slovakia in 1993 from breeding pairs provided by Dr. Vrana, and subsequently maintained by sibling mating.…”

“…The hereditary hypertriglyceridaemic (hHTg) rat manifests several features of the insulin resistance syndrome except obesity [4]. The strain was developed from Wistar rats on the basis of an ability to atIn the last few years the insulin resistance (IR) syndrome has emerged as a potent risk factor for coronary heart disease [1,2].The precise association and the possible causal relationships between the major traits tain a marked rise in plasma triglyceride (Tg) concentration by increased intake of monosaccharides in the diet [5] although the inbred hHTg strain shows increased Tg concentration compared with control strains on normal rat chow [4].…”

“…The strain was developed from Wistar rats on the basis of an ability to atIn the last few years the insulin resistance (IR) syndrome has emerged as a potent risk factor for coronary heart disease [1,2].The precise association and the possible causal relationships between the major traits tain a marked rise in plasma triglyceride (Tg) concentration by increased intake of monosaccharides in the diet [5] although the inbred hHTg strain shows increased Tg concentration compared with control strains on normal rat chow [4]. Further characterisation of the hHTg strain showed that, in addition to being hypertriglyceridaemic it has insulin resistance, hypertension and mild hyperuricaemia [6,7].…”

“…Further characterisation of the hHTg strain showed that, in addition to being hypertriglyceridaemic it has insulin resistance, hypertension and mild hyperuricaemia [6,7]. Although the hHTg strain has been the subject of extensive physiologic and biochemical investigation [4], little is known about the primary genetic lesions responsible for the hypertriglyceridaemia and the other features of the insulin resistance syndrome manifested by the strain. Thus, the main aim of this study was to map the major quantitative trait loci (QTLs) affecting Tg concentration in the hHTg rat and to explore the genetic relationships between plasma Tg, glucose and insulin concentrations s and blood pressure.…”