Chlorthalidone improves endothelial-mediated vascular responses in hypertension complicated by nondiabetic metabolic syndrome.
BACKGROUND
The study was conducted to evaluate the vascular effects of chlorthalidone, a distal tubule-acting natriuretic agent, in hypertensive patients with nondiabetic metabolic syndrome, an insulin-resistant condition characterized by endothelial dysfunction and high risk for diabetes mellitus development.


METHODS
Thirteen untreated hypertensive patients with Adult Treatment Panel-III-defined nondiabetic metabolic syndrome were assigned to 3-month treatment with chlorthalidone. The end-points were baseline and post-treatment evaluation of (1) forearm blood flow (strain-gauge plethysmography) responses to graded intra-arterial acetylcholine infusion to test endothelial-mediated vasomotor function, with sodium nitroprusside as a control for endothelium-independent vasodilatation; (2) minimum forearm vascular resistance, the ratio of mean blood pressure and maximal blood flow in response to 13-minute arterial occlusion, as a hemodynamic correlate of arteriolar structure; and (3) transcapillary albumin escape rate (the 1-hour decay rate of (125)I-albumin, 6-8 microC ev) as a measure of systemic capillary permeability. Additional measurements included baseline and posttreatment lipids, fasting, and postload glucose and insulin as well as the homeostasis model assessment, an index of insulin sensitivity.


RESULTS
Chlorthalidone reduced blood pressure, augmented acetylcholine-mediated vasodilatation, decreased minimum forearm resistance, and slowed the transcapillary albumin escape rate. Metabolic parameters did not change significantly except for an increase in low-density lipoprotein cholesterol levels.


CONCLUSIONS
Chlorthalidone improved endothelial function, reversed abnormal arteriolar structure, and slowed albumin permeation in hypertensive patients with nondiabetic metabolic syndrome.
Dell'Omo
Giulia
G
Dipartimento Cardio Toracico, Università di Pisa, Pisa, Italy.
Penno
Giuseppe
G
Del Prato
Stefano
S
Pedrinelli
Roberto
R
D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000503:physiopathology; D002752:Chlorthalidone / Q000494:pharmacology / Q000627:therapeutic use*; D004232:Diuretics / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy*; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*
D000959:Antihypertensive Agents; D004232:Diuretics; D012709:Serum Albumin; D002752:Chlorthalidone