Interaction between vasodilators and vasopressin in internal mammary artery and clinical significance.
BACKGROUND
Arginine vasopressin (AVP) has recently been demonstrated as an alternative in the treatment of severe refractory vasodilatation in coronary artery bypass grafting. However, AVP may be a spasmogen for graft spasm. We compared the in vitro antispastic effect among calcium-channel antagonists (nifedipine, diltiazem, and verapamil), nitroglycerin, and the highly selective AVP (V1) receptor antagonist [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin.


METHODS
Human internal mammary artery segments (n = 218) were studied in organ baths. The inhibitory effects of the above vasodilators on AVP-mediated contraction were studied in two ways: relaxation with AVP precontraction and depression of the AVP-induced contraction after pretreatment with vasodilators.


RESULTS
All three calcium-channel antagonists caused limited relaxation (18.3%+/-5.4% for nifedipine, n = 11; 22.2%+/-3.8% for verapamil, n = 10; and 26.2%+/-7.5% for diltiazem, n = 9). The plasma concentration of calcium-channel antagonists had no significant depression effect on the AVP-induced contraction. In contrast, [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin caused full (100%, n = 11) and nitroglycerin caused nearly full (93%+/-3%, n = 10) relaxation. Pretreatment with [1-deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin (10(-8), 10(-7), or 10(-6) mol/L, respectively) significantly increased the effective concentration for 50% of the AVP-induced contraction (10(-8.6)+/-10(0.1) mol/L, p = 0.009; 10(-7.8)+/-10(0.07) mol/L, p = 0.000; or 10(-6.9)+/-10(0.11) mol/L, p = 0.000 versus the control, 10(-9.24)+/-10(0.16) mol/L). However, nitroglycerin only slightly depressed the AVP-induced contraction.


CONCLUSIONS
[1-Deaminopenicillamine, 4-valine, 8-D-arginine] vasopressin may provide specific antispastic effect in either prophylaxis or treatment of the AVP-related vasospasm in the internal mammary artery. Nitroglycerin may be effective in treatment but has little effect on prophylaxis. Use of calcium-channel antagonists may have little benefit in AVP-related vasospasm.
Wei
Wei
W
Starr Academic Center, Providence Heart Institute, Department of Surgery, Oregon Health Sciences University, Portland, USA.
Floten
H Storm
HS
He
Guo-Wei
GW
D001127:Arginine Vasopressin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000502:physiology*; D001026:Coronary Artery Bypass; D023903:Coronary Restenosis / Q000503:physiopathology*; D046508:Culture Techniques; D004110:Diltiazem / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008297:Male; D008323:Mammary Arteries / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D009543:Nifedipine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D014665:Vasodilator Agents; D001127:Arginine Vasopressin; C028799:argipressin, deaminopenicillamine(1)-Val(4)-; D014700:Verapamil; D004110:Diltiazem; D005996:Nitroglycerin; D009543:Nifedipine