Dietary Modulation of Sympathetic Activity and Cardiovascular Disease

 
Heinz Rupp.
Molecular Cardiology Laboratory, Department of Internal Medicine and Cardiology, Philipps University of Marburg, Germany
 

Lifestyle factors such as increased caloric intake, diets with a high sodium/potassium ratio and psychosocial stress as well as inadequate physical activity have a key role in the manifestation of primary arterial hypertension. Currently, most antihypertensive strategies are targeted at reducing blood pressure by mechanisms that are not causally related to the influences of deleterious lifestyle factors. Furthermore, the pathophysiological processes during manifestation of hypertension are often not taken into account. The hypothesis was therefore addressed in animal experiments that hypercaloric diets induce hyperkinetic hypertension irrespective of day-night cycle and locomotor activity (Am. J. Physiol., in press). Normotensive rats with implanted radio-telemetry pressure transducers were fed increasing amounts of coconut fat (8%, 16%, 24%, each for 2 weeks) corresponding to 20-47% fat calories. Thereafter, increasing amounts of sucrose (16%, 32%, 50%) and fructose (50%) were added to the 24% fat diet corresponding to 13-40% sugar calories. In contrast to the fat diets, the 32% and 50% sucrose as well as the 50% fructose diets increased (P<0.05) blood pressure (systolic, max. +13 mm Hg; diastolic, max. +4 mm Hg; mean, max. +7 mmHg) and heart rate (max. +50 BPM) irrespective of the day-night cycle and the unaltered locomotor activity. Furthermore, body weight increased (P<0.05) during the 32% and 50% sucrose feeding. The increased blood pressure and heart rate normalized after feeding a regular chow. It is concluded that an excess caloric intake results in hyperkinetic hypertension which precedes established primary hypertension and thus represents an important drug target. Since both heart rate and blood pressure were increased, it can be concluded that sympathetic activity is raised by hypercaloric diets. A sustained release of excess catecholamines aggravates hypertension by a number of processes: i. Remodeling of resistance vessels leading to increased peripheral resistance and thus established hypertension. ii. Release of renin from the kidney with the consecutive formation of angiotensin II (vasoconstriction, vessel remodeling) and aldosterone (increased Na⁺ re-absorption). iii. Vessel rarefaction leading to selective insulin resistance of skeletal muscle. The ensuing hyperinsulinemia promotes Na⁺ re-absorption of the kidney. iv. Atherosclerosis favored by enhanced insulin influences on lipid metabolism (hypertriglyceridemia, LDL increase) vi. Radical injury arising from catecholamine oxidation favoring cytosolic Ca²⁺-overload. Since sympathetic outflow of the brain can be reduced by imidazoline I₁ -receptor agonists, it represents an efficient approach for reducing consequences of lifestyle factors leading to excess catecholamines. Taking into account the fact that the incidence of primary hypertension in the absence of deleterious lifestyle factors, particularly hypercaloric nutrition, would be low, it can be postulated that early interference with excess sympathetic outflow should represent an efficient approach for reducing the manifestation of hypertension as well as prevention of associated cardiovascular disorders (excess catecholamine syndrome).

  
 
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