The endothelium and cyclic guanosine monophosphate in hyperthyroid-induced hypertension.
We investigated the role of endothelium derived relaxing factor (EDRF) and cyclic guanosine monophosphate (cGMP) in the altered vascular reactivity of hyperthyroidism (HT). Rats were given daily injections of triiodothyronine (T3), 50 micrograms/100 g body weight for two weeks, and they had significantly higher serum levels of T3 compared to untreated, control rats (493 +/- 82 vs. 58 +/- 7 ng/dl, p less than 0.05) and significant elevations in their systolic blood pressure (188 +/- 6 vs 126 +/- 3 mm Hg, p less than 0.05). Vascular reactivity was studied in isolated muscle baths; cGMP was measured by RIA. There were no differences in contractile responses to phenylephrine (PE) in isolated aortae from the HT and control rats, but aortae from the HT rats contracted with PE relaxed less to acetylcholine (Ach); the calcium ionophore, A23187; and sodium nitroprusside (SNP). Sensitivity to atrial natriuretic factor (ANF) and 8-Br cGMP was unaltered. Blood vessels from HT rats generated significantly less cGMP in response to Ach, SNP, and ANF. Treatment of the hypertension in the HT rats which hydralazine or propranolol restored the vascular relaxation response to Ach but not SNP; cGMP responses remained blunted. These data suggest that endothelium dependent vasodilators may induce relaxation independent of elevations of cGMP in aortae from HT rats.
Lockette
W
W
Henry Ford Hospital, Detroit, Michigan 48202.
Otsuka
Y
Y
Hirt
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001688:Biological Products / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology*; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology; D006980:Hyperthyroidism / Q000150:complications* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014664:Vasodilation / Q000187:drug effects
D001688:Biological Products; D009599:Nitroprusside; D010656:Phenylephrine; D006830:Hydralazine; D009569:Nitric Oxide; D006152:Cyclic GMP; D000109:Acetylcholine