Effect of angiotensin II on venodilator response to nitroglycerin.
OBJECTIVE
An enhanced circulatory angiotensin II level that results from the administration of nitroglycerin may contribute to the development of nitrate tolerance. Using human hand veins, we investigated whether a subconstricting dose of angiotensin II attenuates the venodilator effect of nitroglycerin, whether pretreatment with losartan influences this effect, and whether angiotensin II also attenuates the venodilator effect of diltiazem.


METHODS
In 9 healthy male subjects, increasing doses (0.5-128 ng/min) of nitroglycerin were infused into the dorsal hand vein pretreated with 0 (control), 0.3, or 1 ng/min of angiotensin II. In 8 healthy male subjects, angiotensin II (0.3 and 1 ng/min) was infused into the vein dilated by nitroglycerin with and without pretreatment with losartan and with diltiazem. The diameter of the vein was measured with a linear variable differential transformer.


RESULTS
The venodilator response of nitroglycerin was significantly suppressed by the pretreatment with angiotensin II; The maximum venodilator effect was dose-dependently decreased, and the infusion rate producing half-maximum response was dose-dependently increased. The venodilation caused by nitroglycerin was decreased by angiotensin II, and this effect was attenuated by pretreatment with losartan. The venodilation caused by diltiazem was also attenuated by angiotensin II, but this attenuating effect was smaller compared with that caused by nitroglycerin.


CONCLUSIONS
These findings suggest that an enhanced angiotensin II level might attenuate the venodilation caused by nitroglycerin and diltiazem, and pretreatment with losartan might decrease the attenuating effect of angiotensin II.
Department of Clinical Pharmacology, Jichi Medical School.
K
K
Harada
K
K
Sugimoto
A
A
Kawaguchi
M
M
Ohmori
A
A
Fujimura
D000328:Adult; D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007262:Infusions, Intravenous; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D005996:Nitroglycerin / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D004110:Diltiazem; D005996:Nitroglycerin; D019808:Losartan