Chronic exogenous hyperinsulinaemia without sugar supplementation: acute salt-sensitive hypertension without changes...

To study the effects of chronic insulin administration without sugar supplementation on blood pressure and response to acute saline loading in normal rats.

Comparison of blood pressure, insulin and glucose levels in 24 insulin-treated and 12 control rats on regular rat chow (not supplemented with sugar).

Sustained-release insulin implants (or sham implantation for the control rats) were administered subcutaneously. The sustained-release insulin implant size was gradually increased. Tail-cuff systolic blood pressure, insulin and glucose were measured twice a week for 8 weeks, after which intra-arterial blood pressure was recorded under resting conditions and 2 h after saline loading in seven insulin-treated and seven control rats.

Insulin-treated rats had a 1.2- to twofold increase in insulin without hypoglycaemia, a small but significant increase in glucose levels being found at weeks 6 and 8. When the rats were killed (week 8) triglyceride and fructosamine levels were increased in the insulin-treated rats in comparison with controls. Neither tail-cuff systolic blood pressure nor resting intra-arterial blood pressure differed between the two groups. However, acute saline loading resulted in significantly higher blood pressure in the insulin-treated rats, without altering renal Na+ excretion.

It is possible to produce mild hyperinsulinaemia without hypoglycaemia by gradually increasing subcutaneous sustained-release insulin administration without sugar supplementation. Such hyperinsulinaemia is associated with significantly higher glucose, fructosamine and triglyceride levels, and normal tail-cuff and resting intra-arterial blood pressure. Insulin may induce intolerance to acute volume loading that is not associated with Na+ retention.