CHRONIC HYPERINSULINEMIA AND HYPERTENSION - THE ROLE OF THE SYMPATHETIC NERVOUS-SYSTEM

Objective: To determine the implication of the sympathetic nervous sys tem in the relationship observed between insulin resistance and hypert ension. Design: Rats were chronically treated with insulin for 12 days by subcutaneously implanted osmotic pumps and given 10% glucose in th eir drinking water. A separate group oi rats also received glucose onl y, and control rats received tap water. Results: Physiological hyperin sulinaemia (1.5 and 4.5 mU/kg per min insulin) increased mean arterial pressure by approximately 10 mmHg and heart rate by 60 beats/min, and supraphysiological insulinaemia (9 mU/kg per min) did not produce add itional haemodynamic effects. Insulin-treated rats developed insulin r esistance, as shown by an intravenous glucose-tolerance test. Glucose treatment alone induced intermediate haemodynamic and metabolic respon ses. Plasma noradrenaline levels rose slightly in insulin-treated rats and were positively correlated with mean arterial pressure but not wi th insulinaemia, even though insulinaemia was also correlated with mea n arterial pressure. The reflex sympathetic activation during hypotens ion revealed, in the presence of a noradrenaline uptake antagonist, th at insulin increases noradrenaline release but also enhances noradrena line uptake. Chronic hyperinsulinaemia did not alter the sympathetic v ascular and cardiac responses, as assessed by the measurement of the s econd messengers produced by activation of alpha(1)- or beta-adrenergi c receptor pathways. Conclusion: Chronic euglycaemic hyperinsulinaemia seems to modify sympathetic activity through several mechanisms, and this action could participate in the elevation of blood pressure obser ved in this rat model.