Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles.
OBJECTIVE
Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones.


METHODS
We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography.


RESULTS
There was no significant improvement in endothelium-dependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol.


CONCLUSIONS
Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactone-induced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.
Swaminathan
K
K
Division of Medicine and Therapeutics, Ninewells Hospital and Medical School, Dundee, DD1 9SY, UK. krishnan.swaminathan@nhs.net
Davies
J
J
George
J
J
Rajendra
N S
NS
Morris
A D
AD
Struthers
A D
AD
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D015992:Body Mass Index; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000188:drug therapy*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood
D000450:Aldosterone; D000804:Angiotensin II; D001786:Blood Glucose; D005346:Fibroblast Growth Factors; D006442:Glycated Hemoglobin; D006854:Hydrocortisone; D020097:Natriuretic Peptide, Brain