Chronic hyperinsulinaemia and hypertension: the role of the sympathetic nervous system.
OBJECTIVE
To determine the implication of the sympathetic nervous system in the relationship observed between insulin resistance and hypertension.


METHODS
Rats were chronically treated with insulin for 12 days by subcutaneously implanted osmotic pumps and given 10% glucose in their drinking water. A separate group of rats also received glucose only, and control rats received tap water.


RESULTS
Physiological hyperinsulinaemia (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 additional haemodynamic effects. Insulin-treated rats developed insulin resistance, as shown by an intravenous glucose-tolerance test. Glucose treatment alone induced intermediate haemodynamic and metabolic responses. Plasma noradrenaline levels rose slightly in insulin-treated rats and were positively correlated with mean arterial pressure but not with insulinaemia, even though insulinaemia was also correlated with mean arterial pressure. The reflex sympathetic activation during hypotension revealed, in the presence of a noradrenaline uptake antagonist, that insulin increases noradrenaline release but also enhances noradrenaline uptake. Chronic hyperinsulinaemia did not alter the sympathetic vascular and cardiac responses, as assessed by the measurement of the second messengers produced by activation of alpha 1- or beta-adrenergic receptor pathways.


CONCLUSIONS
Chronic euglycaemic hyperinsulinaemia seems to modify sympathetic activity through several mechanisms, and this action could participate in the elevation of blood pressure observed in this rat model.
Moreau
P
P
Faculty of Pharmacy, University of Montreal, Quebec, Canada.
Lamarche
L
L
Laflamme
A K
AK
Calderone
A
A
Yamaguchi
N
N
de Champlain
J
J
D000818:Animals; D001158:Arteries / Q000378:metabolism; D005951:Glucose Tolerance Test; D006946:Hyperinsulinism / Q000150:complications* / Q000378:metabolism; D006973:Hypertension / Q000209:etiology*; D007328:Insulin / Q000008:administration & dosage; D008297:Male; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000378:metabolism; D015290:Second Messenger Systems; D013564:Sympathetic Nervous System / Q000378:metabolism* / Q000503:physiopathology
D007328:Insulin; D011941:Receptors, Adrenergic; D009638:Norepinephrine