Altered aortic production of 6-keto-prostaglandin F1 alpha from aldosterone-salt hypertensive rats.
Supersensitivity of vascular smooth muscle to catecholamines in aldosterone-salt hypertensive rats appears to reside beyond the alpha 1-adrenoceptor. The objective of this study was to assess the norepinephrine-stimulated production of arachidonic acid metabolites by aorta from control-salt rats (CSR) and aldosterone-salt hypertensive rats (AHR) to determine whether these metabolites might contribute to the altered sensitivity. Norepinephrine increased in a time-dependent manner the production of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) by the aortae of CSR. Production was an alpha 1-adrenoceptor-mediated event since it was inhibited greatly by prazosin but not by yohimbine. Basal values of the metabolites did not differ for 6-keto-PGF1 alpha and TXB2, but were higher in AHR compared with CSR for PGE2. The norepinephrine concentration-response curve for 6-keto-PGF1 alpha was shifted significantly to the right for the AHR group compared with CSR (EC50 = 2.30 +/- 0.55 and 0.29 +/- 0.07 microM, respectively) indicating decreased production of norepinephrine-stimulated prostaglandin I2 in AHR. The norepinephrine-stimulated TXB2 concentration-response curves for AHR and CSR were similar. Indomethacin was an effective inhibitor of TXB2 and 6-keto-PGF1 alpha production in both. Norepinephrine-stimulated contraction was significantly affected by indomethacin in CSR but not in AHR. Whereas we observed an attenuation of a norepinephrine-stimulated vasodilatory substance in aortae of AHR compared with CSR, the effect of attenuation on vascular activity is presently unclear.
Jones
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SB
Department of Physiology, University of Missouri, Columbia 65212.
Liu
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Y
Jones
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AW
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism*; D000450:Aldosterone; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D015232:Dinoprostone / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism*; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000502:physiology / Q000503:physiopathology*; D009638:Norepinephrine / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012982:Sodium, Dietary; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011465:Prostaglandins, Synthetic; D012982:Sodium, Dietary; D000450:Aldosterone; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; C026678:carboprostacyclin; C045749:SQ 29548; D011464:Epoprostenol; D015232:Dinoprostone; D009638:Norepinephrine; D007213:Indomethacin