The pathogenesis of hypertension in obese subjects

Obese subjects are at an increased risk of becoming hypertensive and vice versa. Essential hypertension and obesity are commonly accompanied by insulin resistance (defined as impaired insulin-mediated glucose disposal) and hyperinsulinaemia. In the offspring of patients with essential hypertension, insulin resistance and hyperinsulinaemia, as well as related increases in serum low density lipoproteins and triglycerides, often occur prior to the development of essential hypertension, overweight or central redistribution of body fat. Moreover, once obesity, and in particular central obesity, is present, insulin resistance is more marked in hypertensive than in normotensive obese subjects. Hyperinsulinaemia and/or insulin resistance in turn promote body fat deposition and impaired glucose tolerance. This cycle helps to explain why a familial predisposition to essential hypertension poses an increased risk of developing not only hypertension but also dyslipidaemia, obesity and non-insulin-dependent (type 2) diabetes. It is still unclear whether insulin resistance and/or hyperinsulinaemia also promote hypertension per se. Regardless of insulin's exact pathogenic role, obesity and/or a high dietary intake of carbohydrates, salt, etc. can induce several potential pressor mechanisms: 1) higher plasma noradrenaline (norepinephrine) and adrenaline (epinephrine) levels, suggesting a higher sympathetic tone in obese than in nonobese subjects, and in hypertensive obese than in normotensive obese subjects; 2) similarly, a tendency to hyperaldosteronism, with largely normal plasma renin activity, in obese hypertensive patients; 3) enhanced sensitivity of blood pressure to salt; 4) increased total blood volume (although it is normal relative to body surface area), leading to increased cardiac output and eventually eccentric left ventricular hypertrophy; and 5) increased cytosolic free Ca++ levels and reduced intracellular Mg++ levels in the blood cells of obese hypertensive patients and patients with non-insulin-dependent diabetes, although this finding cannot necessarily be extrapolated to cationic levels in vascular muscle cells. Total peripheral vascular resistance is usually low in normotensive obese subjects and rises with the development of hypertension; compared with lean patients with essential hypertension, obese hypertensive patients tend to have a slightly lower level of total peripheral vasoconstriction and a slightly higher cardiac output. Considering the intimate association between essential hypertension and obesity, as well as the prevalence and prognostic relevance of this combination, the spectrum of accompanying metabolic and cardiovascular abnormalities deserves careful consideration in the evaluation of therapeutic care for such patients.