Reduced endothelium-dependent vasodilation by acetylcholine and bradykinin in isolated nitroglycerin-tolerant blood vessels.
1. Rings of porcine pulmonary arteries were mounted in tissue organ baths and incubated in physiological solution. The rings were allowed to equilibrate for > 1 hr under a resting tension of 1.0 g. The presence of endothelium was confirmed by 10(-6) M acetylcholine (ACh)-induced relaxation (60-80%) of 10(-6) M norepinephrine (NE) contraction. 2. Relaxation response generated by nitroglycerin (NTG) (10(-9) - 10(-5) M), ACh (10(-9) - 10(-5) M), bradykinin (BK) (10(-13) - 10(-6) M) and nitric oxide (NO) after NE (10(-6) M) contraction was compared before and after 1 hr treatment of NTG (5 x 10(-4) M). Then tissues were pretreated with NG-monomethyl-L-arginine (LNMMA) (10(-4) M) each before and after NTG treatment respectively, and ACh-induced relaxation was compared. 3. After 1 hr treatment with 5 x 10(-4) M NTG, the relaxation response of NTG at concentrations > 10(-7) M was attenuated significantly. This indicates that 1 hr treatment with 5 x 10(-4) M NTG induces NTG tolerance in isolated porcine pulmonary arterial rings. 4. The relaxation response of ACh at concentrations > 10(-7) M was attenuated significantly after NTG tolerance induction. 5. Relaxation response of BK at concentrations > 10(-10) M was attenuated significantly after NTG tolerance induction. 6. NTG tolerance had no effect on NO-induced vascular smooth muscle relaxation. 7. The relaxation response of ACh pretreated with LNMMA at concentrations higher than 10(-7) M was attenuated after NTG tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)
Fukazawa
M
M
Third Department of Internal Medicine, Toho University School of Medicine, Ohashi Hospital, Tokyo, Japan.
Namiki
A
A
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology*; D004361:Drug Tolerance; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D005996:Nitroglycerin / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D001120:Arginine; D005996:Nitroglycerin; D000109:Acetylcholine; D001920:Bradykinin