Plasma levels of nitric oxide and related vasoactive factors following long-term treatment with angiotensin-converting enzyme inhibitor in patients with essential hypertension.
Several mechanisms other than the inhibition of systemic and local formation of angiotensin II (Ang II) have been proposed to play a role in mediating the hypotensive effects of angiotensin-converting enzyme (ACE) inhibitors. In the present study, we measured plasma levels of nitric oxide (NO) and the related vasoactive factors bradykinin, 6-keto prostaglandin F1alpha (6-keto PGF1alpha) a stable metabolite of prostacyclin, and cyclic guanosine-3',5'-monophosphate (cGMP) before and after a 4-week treatment with the ACE inhibitor lisinopril in 17 patients with essential hypertension. Plasma NO levels were measured by the Griess method after conversion of nitrate to nitrite. Long-term lisinopril treatment significantly reduced blood pressure and increased plasma NO and 6-keto PGF1alpha. The treatment also tended to increase plasma levels of bradykinin and cGMP, but not to a significant extent. The posttreatment NO level was inversely correlated with posttreatment systolic, diastolic, and mean blood pressure (n = 17, r= -.68, P< .01, n = 17, r= -.54, P < .05, and n = 17, r= -.66, P< .01, respectively). The posttreatment bradykinin level was also modestly correlated with posttreatment systolic and mean blood pressure (n = 17, r = -.51, P < .05 and n = 17, r = -.55, P < .05, respectively). In contrast, posttreatment 6-keto PGF1alpha and cGMP levels were not correlated with posttreatment systolic, diastolic, or mean blood pressure. These findings raise the possibility that increased formation of NO and bradykinin, as well as inhibition of the renin-angiotensin system, contribute to the hypotensive effect of the ACE inhibitor observed in our hypertensive patients.
Kohno
M
M
First Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan.
Yokokawa
K
K
Minami
M
M
Yasunari
K
K
Maeda
K
K
Kano
H
H
Hanehira
T
T
Yoshikawa
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D001920:Bradykinin / Q000097:blood*; D006152:Cyclic GMP / Q000097:blood; D003971:Diastole / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000097:blood*; D011674:Pulse; D012044:Regression Analysis; D012083:Renin / Q000097:blood; D013599:Systole / Q000187:drug effects; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D009569:Nitric Oxide; D015121:6-Ketoprostaglandin F1 alpha; D012083:Renin; D006152:Cyclic GMP; D001920:Bradykinin