Effect of angiotensin-converting enzyme inhibitors and nitroxy groups on human coronary resistance vessels in vitro.
We investigated the interaction between nitroxy groups and angiotensin-converting enzyme (ACE) inhibitors to assess the role of sulfhydryl groups and adenosine triphosphate (ATP)-sensitive potassium channels in vasodilation of human coronary resistance vessels in vitro. Coronary resistance vessels were resected from the right atrial appendage of 27 patients undergoing open heart surgery. The vessel ends were inserted into a microglass pipette with the internal pressure maintained at 40 mm Hg. Nitroglycerin did not change the vasoresponse, whereas nicorandil induced a concentration-dependent vasodilation that was not affected by methylene blue, but was markedly inhibited by glibenclamide. The ACE inhibitors, captopril, with a sulfhydryl group (1 x 10(-6) M), and enalaprilat, without a sulfhydryl group (1 x 10(-6) M), were added to either nitroglycerin or nicorandil to assess the incremental response of the sulfhydryl group to vasodilation. The addition of captopril or L-cysteine (1 x 10(-6) M) enhanced the activity of both nitroglycerin and nicorandil, whereas addition of enalaprilat did not. The responses of nicorandil and nitroglycerin to captopril and were similar. Cromakalim was not enhanced by L-cysteine or captopril. The response of nitroglycerin was not enhanced by captopril or L-cysteine after addition of N(G)-monomethyl-L-ARGININE (L-NMMA). Both nitroglycerin and nicorandil exhibited an increase in vasodilation in the presence of an ACE inhibitor containing a sulfhydryl group. The mechanism of the vasodilatory action in the coronary resistance vessels may involve the opening of an ATP-sensitive potassium channel and subsequent guanylate cyclase activation. These interactions have important clinical implications.
Takahashi
K
K
First Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan. keiko@hyo-med.ac.jp
Ohyanagi
M
M
Kobayashi
S
S
Iwasaki
T
T
Miyamoto
T
T
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D019806:Cromakalim / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects; D020108:Nicorandil / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D013314:Stress, Mechanical; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D014665:Vasodilator Agents; D019806:Cromakalim; D020108:Nicorandil; D005996:Nitroglycerin