Immediate but not long-term intranasal administration of insulin raises blood pressure in human beings

Intranasal administration of insulin has been shown to influence neuroendocrine functions via an effect on central nervous mechanisms. Because insulin, in particular when infused into cerebral arteries, induces blood pressure (BP) elevation by an unknown mechanism, we investigated whether insulin exerts similar effects on BP after intranasal administration. To evaluate the immediate effects of insulin on BP, 20 IU of human insulin was intranasally administered every 10 minutes over a 2-hour period. Blood pressure, heart rate, and muscular sympathetic nervous activity (MSNA) were continuously monitored. For evaluating the effects of subchronic administration of insulin, changes during and after 8 weeks of treatment with 160 IU insulin/d on BP were monitored. Compared with placebo, the immediate nasal administration of insulin raised diastolic BP (12.21% ± 5.10%; P < .05), mean arterial BP (10.81% ± 4.32%; P < .04), and systolic BP (9.53% ± 4.66%; P < .08), whereas MSNA and heart rate were unaffected. In contrast, prolonged intranasal insulin administration did not affect BP (P > .62 for all comparisons). The immediate increase in BP in the face of an unsuppressed MSNA after insulin suggests that intranasal insulin transiently changes the baroreflex set point. Thus, data suggest that intranasal insulin administration affects BP regulatory centers in the brain. However, the effect is not observed with prolonged administration of the hormone, suggesting the emergence of counterregulatory processes.