Endothelial modulation of norepinephrine-induced constriction of rat aorta at normal and high CO2 tensions.
Endothelial modulation of norepinephrine (NE)-induced constriction of the isolated rat aorta was studied at normal (PCO2, 41 +/- 0 mmHg) and high CO2 tensions (PCO2, 91 +/- 1 mmHg). In preparations with intact endothelium, increased CO2 tension resulted in rightward shift of the NE dose-response curve with attenuation of maximal contraction. This effect of CO2 was not modified by indomethacin. Treatment with hemoglobin or rubbing of the endothelium meant that increased CO2 tension still resulted in rightward shift of the NE dose-response curve but without altering the maximal contractile response. The basal guanosine 3',5'-cyclic monophosphate (cGMP) levels in control and NE-treated aortic preparations were not affected by increasing the CO2 tension. Thus the inhibitory action of CO2 on NE-induced contraction in the presence of endothelium may not be derived from facilitation of endothelium-derived relaxation factor (EDRF)-induced cGMP synthesis. Increasing the CO2 tension attenuated the sustained contraction induced by the addition of NE and Ca2+ (2.5 mM) to intact endothelium preparations previously bathed in Ca2(+)-free solution. Further addition of Ca2+ (total 5.0 mM) did not increase the contraction. These findings suggest that the intrinsic activity of NE is greatly modified by endothelium at a high CO2 tension. Vasodilation during hypercapnia may be induced at least in part by synergistic actions of EDRF and CO2 on smooth muscle cells.
Fukuda
S
S
Department of Anesthesiology, Niigata University, School of Medicine, Japan.
Matsumoto
M
M
Nishimura
N
N
Fujiwara
N
N
Shimoji
K
K
Takeshita
H
H
Lee
T J
TJ
D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002245:Carbon Dioxide / Q000097:blood*; D004730:Endothelium, Vascular / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D009712:Nucleotides, Cyclic / Q000378:metabolism; D010313:Partial Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012701:Serotonin / Q000494:pharmacology; D014661:Vasoconstriction
D009712:Nucleotides, Cyclic; D002245:Carbon Dioxide; D012701:Serotonin; D002118:Calcium; D009638:Norepinephrine