The effect of norepinephrine on aortic 42K turnover during deoxycorticosterone acetate hypertension and antihypertensive therapy in the rat.
We studied the effects of norepinephrine on 42K turnover in aorta isolated from rats. The rats were given saline to drink and were made hypertensive by injections of deoxycorticosterone acetate (DOC). Other groups of rats received in addition either 6-hydroxydopamine (6-OH-DA) or a regimen of antihypertensives (Anti-Hy) consisting of reserpine, hydrochlorothiazide, and hydralazine. The weight, length, wall thickness, and circumference of the aorta also were measured. DOC hypertension was associated with increased 42K turnover (rate constant for DOC = 0.0164 +/- 0.0009 vs. 0.0090 +/- 0.0002 min-1 in controls). The responses of 42K turnover to low doses of norepinephrine (NE) were increased in DOC with an ED50 of 3.5 +/- 0.8 X 10(-9) vs. 2.7 +/- 0.5 X 10(-8) M in controls. The aortic weight, weight/length, and wall thickness were also increased. Rats treated with DOC plus 6-OH-DA had lower blood pressure and smaller changes in aortic dimensions; however 42K turnover and response to NE were similar to those of the DOC group. The Anti-Hv group exhibited only small increase in 42K turnover and aortic dimensions when compared to controls. It is concluded that DOC hypertension is associated with increased response of 42K turnover to NE which in turn may contribute to increased responses reported for contraction. The Anti-Hy regimen was more effective than 6-OH-DA in reducing the increased 42K turnover and response to NE associated with DOC hypertension.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001011:Aorta / Q000378:metabolism; D001158:Arteries / Q000378:metabolism*; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000627:therapeutic use; D006852:Hydrochlorothiazide / Q000627:therapeutic use; D006892:Hydroxydopamines / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D009929:Organ Size; D011188:Potassium / Q000378:metabolism*; D011197:Potassium Radioisotopes; D051381:Rats; D012110:Reserpine / Q000627:therapeutic use
D000959:Antihypertensive Agents; D006892:Hydroxydopamines; D011197:Potassium Radioisotopes; D006852:Hydrochlorothiazide; D006830:Hydralazine; D003900:Desoxycorticosterone; D012110:Reserpine; D011188:Potassium; D009638:Norepinephrine