Characterization of the antihypertensive effect of a thiazide diuretic in angiotensin II-induced hypertension.
OBJECTIVE
The antihypertensive effect of thiazide diuretics in angiotensin II induced hypertension has never been characterized. In the current study, we sought to determine the effect of a thiazide diuretic on arterial pressure and renal fluid excretion in rats receiving a chronic intravenous infusion of angiotensin II while on fixed normal or high sodium intakes.


METHODS
Male rats were chronically instrumented with arterial and venous catheters for drug injection and direct daily measurements of blood pressure and heart rate. Rats were maintained on high salt intake (HS), 6 mEq/day, or on normal salt intake (NS), 2 mEq/day. Rats were randomly assigned to four groups: HS and NS with 15 day angiotensin II infusion (5 ng/min) and HS and NS without angiotensin II infusion. Trichlormethiazide (TCM), a thiazide diuretic, was orally administered, approximately 10 mg/kg per day, for the middle 5 days of angiotensin II infusion.


RESULTS
Only HS rats receiving angiotensin II infusion became hypertensive. Angiotensin II infusion did not produce changes in heart rate, sodium balance or water balance. Chronic administration of TCM significantly reduced mean arterial pressure (MAP) within 24 h in HS rats receiving angiotensin II, but did not affect MAP in any other group. TCM produced a similar loss of Na+ and water in all rats. Blood volumes and plasma electrolytes did not change during the study.


CONCLUSIONS
The antihypertensive effects of thiazide diuretics are not due exclusively to volume depletion. We propose that salt and water loss caused by TCM may lower MAP by impairment of salt-sensitive pressor mechanisms activated by angiotensin II.
Ballew
J R
JR
Department of Pharmacology, Michigan State University, East Lansing, Michigan 48824, USA.
Fink
G D
GD
D000804:Angiotensin II; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004232:Diuretics; D004334:Drug Administration Schedule; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D049993:Sodium Chloride Symporter Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D014237:Trichlormethiazide / Q000008:administration & dosage / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D004232:Diuretics; D049993:Sodium Chloride Symporter Inhibitors; D000804:Angiotensin II; D014237:Trichlormethiazide