Application of prazosin is associated with an increase of insulin sensitivity in obese patients with hypertension

Abstract

The aim of this study was to determine whether insulin sensitivity measured by the euglycaemic insulin clamp technique is lower in patients with primary hypertension than in matched healthy control subjects, and whether this sensitivity was affected after 12 weeks of antihypertensive treatment with the alpha 1-adrenoceptor blocking drug prazosin. Twelve moderately obese normoglycaemic patients (four men), with hypertension not previously treated with pharmacological agents and diastolic blood pressure above 100 mm Hg, and 12 healthy matched control subjects participated. Supine blood pressure decreased 12/5 mm Hg (p less than 0.01) and standing blood pressure 14/9 mm Hg (p = 0.001) during prazosin treatment (mean dosage 5.3 +/- 1.6 mg/day (SD]. During euglycaemic insulin clamp studies the control subjects showed a higher mean glucose uptake than the untreated hypertensive patients (7.5 +/- 1.0 and 5.8 +/- 1.9 mg.kg b.w.-1.min-1, respectively, p less than 0.01). During prazosin treatment there was no significant difference between the hypertensive patients and the control subjects in this respect (6.6 +/- 2.8 and 7.5 +/- 1.0, respectively, p = 0.21). During prazosin treatment, however, the disappearance rate of glucose decreased during the intravenous glucose tolerance test (from 1.7 +/- 0.9 to 1.3 +/- 0.6, p less than 0.02) and the area under the glucose concentration-time curve decreased by 38% (from 473 +/- 119 to 294 +/- 99, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of Antihypertensive Treatment on Platelet Function in Essential Hypertension.

“…They indicated that the a1-blockers inhibit Ca2+ mobilization in platelets and that this mechanism may be the means by which a1-blockers inhibit platelet aggregation. The a1-blocker is reported to improve insulin sensitivity (18) and lipid metabolism (19) in patients with essential hypertension. The mechanisms underlying these effects may be explained by the a1-blocker's catecholamine blocking effects and vasodilator effects (18).…”

“…The a1-blocker is reported to improve insulin sensitivity (18) and lipid metabolism (19) in patients with essential hypertension. The mechanisms underlying these effects may be explained by the a1-blocker's catecholamine blocking effects and vasodilator effects (18). Although the exact mechanisms of our observation and those of others indicating the inhibitory effect of an a-blocker on platelet function remain to be clarified, it appears that the a-blocker's effect on platelets, insulin sensitivity, and lipid metabolism may be beneficial in preventing hypertensive end organ damage.…”

Metformin as additional therapy in adolescents with poorly controlled type 1 diabetes: randomised placebo-controlled trial with aspects on insulin sensitivity

“…The amount of glucose infused during the last 60 min after a steady-state was achieved was calculated (M) and was related to the mean insulin concentration for the estimation of insulin sensitivity (M/I) (16,18). Both M and M/I are estimations of the total peripheral insulin sensitivity regarding the glucose metabolism, based on the assumption that the hyperinsulinaemic level totally inhibits glucose production from the liver (19).…”

Do angiotensin converting enzyme inhibitors represent a progress in hypertension care in diabetes mellitus?

“…Insulin resistance not only occurs in manifest Type 2 diabetes, but also in impaired glucose tolerance, obesity, essential hypertension and even in 25% of subjects with normal glucose tolerance [9], i.e. in a variety of "pre-diabetic states".…”

“…Improvement of insulin sensitivity has been suggested not only for ACE inhibitors but also for prazosin [9], metoprolol [10] and atenolol [10]. However, these were placebo controlled trials and a non-specific effect of blood pressure reduction independent of the antihypertensive drug used has not been excluded.…”