The hypertension-prone man: A study on the pathogenesis of hypertension with regard to insulin sensitivity

Research output: ThesisDoctoral Thesis (compilation)

Bibtex

@phdthesis{c0797b46584941eb843515a64f9bc495,
title = "The hypertension-prone man: A study on the pathogenesis of hypertension with regard to insulin sensitivity",
abstract = "Hypertensive individuals, even non-obese, have been shown to be resistant to the insulin-mediated glucose uptake in peripheral tissues {mainly skeletal muscle}. The aim of this study was to investigate hypothetical pathophysiological mechanisms for the development of hypertension with regard to insulin sensitivity in normotensive men with a family history of hypertension (RELs) as compared to men with no such family history (CONs). RELs were resistant to the insulin-mediated glucose uptake and had a lower maximal oxygen uptake. There was a positive correlation between insulin sensitivity and maximal oxygen uptake in both groups. When compensating for differences in maximal oxygen uptake the differences in insulin sensitivity disappeared. RELs had retained insulin-mediated forearm vasodilation. Thus, skeletal muscle blood flow did not seem to be the major determinant of glucose disposal. On the other hand, the positive correlation between glucose disposal and the decrease in forearm vascular resistance found in RELs suggests that insulin-induced vasodilation may be a limiting factor for glucose uptake in insulin-resistant individuals. REL had less capillaries per FTb muscle fiber and marginally greater diffusion distance from the capillary to the muscle cell, which may be a contributory factor to low insulin sensitivity in RELs. There was no difference in glycogen synthase activity between the groups so this can not explain the lower glucose disposal rate in RELs. Insulin sensitivity may also partly be influenced by the effect of testosterone on glycogen synthase activity. REL had lower concentrations of SHBG and total testosterone, but similar free testosterone levels. The most likely explanation for this is that the SHBG level is primarily influenced by the relative hyperinsulinemia induced by the lower insulin sensitivity. Serum triglycerides and LDL/HDL ratio were elevated in RELs RELs had retained insulin-stimulated tubular sodium reabsorption, which in a hyperinsulinemic state may cause sodium retention. The lack of suppresion of aldosterone secretion during insulin infusion in RELs may also add to the enhancement of sodium retention and contribute to the development of hypertension. RELs had decreased fibrinolysis but also higher levels of several anti-coagulant proteins. The clinical implication for these disturbances for future development of cardiovascular disease warrants additional studies. In conclusion, men with a family history of hypertension are insulin resistant, have a lower physical capacity, and fibrinolytic capacity, as well as elevated blood lipids as compared to controls, a constellation that may make them more prone to develop cardiovascular disease. The lower capillarisation of skeletal muscle and a more insulin-resistant muscle fibre profile may partly explain the lower insulin sensitivity. The retained antinatriuretic effect of insulin and decreased aldosterone suppression during insulin infusion may enhance sodium retention and initiate blood pressure elevation.",
keywords = "Cardiovascular system, sex steroid hormones, sodium retention, glycogen synthase, fibrinolysis, physical fitness, blood flow, insulin resistance, muscle fibres, Kardiovaskul{\"a}ra systemet",
author = "Tomas Endre",
note = "Defence details Date: 1997-05-12 Time: 10:15 Place: Department of Medicine, lecture hall, University Hospital MAS, Malm{\"o}, Sweden. External reviewer(s) Name: Landin-Wilhelmsen, Kerstin Title: [unknown] Affiliation: [unknown] ---",
year = "1997",
language = "English",
publisher = "Department of Medicine, Lund University",
school = "Department of Clinical Sciences, Malm{\"o}",

}