The effects of hyperinsulinaemia on myocardial mass, blood pressure regulation and central haemodynamics in rats.
Left ventricular hypertrophy is a condition with high mortality. An association with insulin resistance and hyperinsulinaemia has recently been suggested. The aim of this study was to examine the effects of isolated hyperinsulinaemia on cardiac weight and haemodynamic regulation. Rats were exposed to hyperinsulinaemia for 7 weeks after adrenalectomy with corticosterone substitution and continuous infusion of propranolol to control counter-regulatory mechanism (n = 15) (AIP group). Hypoglycaemia was prevented by glucose in the drinking water. Hyperinsulinaemic (AIP) rats were heavier and had increased relative masses of the myocardium (left ventricle 17% and right ventricle 20%), kidneys and adipose tissues in comparison with normoinsulinaemic adrenalectomized, corticosterone- and propranolol-treated controls (AP) (n = 10). Blood pressure in the insulin-exposed animals, measured weekly by the tail-cuff method in conscious rats, was not different from (AP) controls over 5 weeks, but increased in the sixth week. At the end of the seventh experimental week, blood pressure measured intra-arterially was also found to be elevated. Heart rate was not changed but total peripheral resistance was about twice that of controls (P < 0.001). Cardiac output and stroke volume was 30-40% lower in the AIP rats (P < 0.05). It is concluded that exposure to elevated insulin levels with control of counter-regulating mechanisms from beta-adrenergic mechanisms and adrenals is not immediately followed by blood pressure elevation. It is, therefore, suggested that early onset of blood pressure elevation after insulin exposure might be caused by insulin counter-regulatory events, causing both insulin resistance and blood pressure elevation. The long-term adaptations may involve a direct influence by insulin as a 'trophic factor' on myocardial and on peripheral resistance levels, followed by increased blood pressure, decreased cardiac and stroke volume.
Holmäng
A
A
Wallenberg Laboratory, Department of Heart and Lung Diseases, Sahlgrenska University Hospital, Göteberg, Sweden.
Yoshida
N
N
Jennische
E
E
Waldenström
A
A
Björntorp
P
P
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D005260:Female; D006321:Heart / Q000033:anatomy & histology*; D006439:Hemodynamics / Q000187:drug effects*; D006946:Hyperinsulinism / Q000503:physiopathology*; D006973:Hypertension / Q000209:etiology; D017379:Hypertrophy, Left Ventricular / Q000209:etiology; D007333:Insulin Resistance / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013318:Stroke Volume / Q000187:drug effects