Anderson R J, Berl T, McDonald K D, Schrier R W
J Clin Invest. 1975 Aug;56(2):420-6. doi: 10.1172/JCI108108.
These studies were undertaken to examine whether an antagonism between vasopressin and prostaglandin occurs in vivo in the mammalian kidney. All experiments were performed in steroid-replaced hypophysectonized dogs undergoing a water diuresis. In the first group of studied the effect of two consecutive intravenous doses (100 mU) of vasopressin was examined. The second dose of vasopressin was preceded by an injection of the carrier solution for solubilizing indomethacin or neclofenamate. No enhancement of the antidiuretic effect of the second dose of vasopressin was observed as urinary osmolality (Uosm) increased from 92 +/- 5 to 252 +/- 18 mosmol/kg H2O (P less than 0.0001) after the first dose and from 109 +/- 8 to 209 +/- 10 mosmol/kg H2O (P less than 0.001) after the second dose of vasopressin. In another group of studies the second dose of vasopressin was preceded by the administration of a potent inhibitor of prostaglandin synthesis, indomethacin (2 mg/kg). The Uosm increased from 93 +/- 9 to 244 +/- 33 mosmol/kg H2O (P less than 0.001) after the first dose of vasopressin, but after the second dose of vasopressin the Uosm increased to a significantly greater degree from 106 +/- 14 to 702 +/- 69 mosmol/kg H2O (P less than 0.001). In a third group of studies the antidiuretic effect of the same 100-mU dose of vasopressin was examined before and after the administration of meclofenamate (2 mg/kg), an inhibitor of prostaglandin synthesis which is chemically dissimilar from indomethacin. Uosm increased from 83+/-7 to 216+/-16 mosmol/kg H2O (P less than 0.001) after the first dose and from 101 +/- 8 to 734 +/- 86 mosomol/kg H2O (P less than 0.001) after the second dose of vasopressin. As in the indomethacin studies this enhancement in the antidiuretic effects of vasopressin after inhibition of prostaglanding synthesis was highly significant (P less than 0.001). These results therefore implicate a physiological role of prostaglandin in modulating the hydroosmotic effect of vasopressin in the mammalian kidney.
进行这些研究是为了检验血管升压素与前列腺素之间的拮抗作用在哺乳动物肾脏内是否会在体内发生。所有实验均在接受水利尿的经类固醇替代的垂体切除犬身上进行。在第一组研究中，检测了连续两次静脉注射（100 mU）血管升压素的效果。第二次注射血管升压素之前，先注射了用于溶解吲哚美辛或氯苯那敏的载体溶液。在第一次注射血管升压素后，尿渗透压（Uosm）从92±5升高至252±18 mosmol/kg H₂O（P＜0.0001），第二次注射血管升压素后，尿渗透压从109±8升高至209±10 mosmol/kg H₂O（P＜0.001），未观察到第二次注射血管升压素的抗利尿作用增强。在另一组研究中，第二次注射血管升压素之前，先给予了前列腺素合成的强效抑制剂吲哚美辛（2 mg/kg）。第一次注射血管升压素后，尿渗透压从93±9升高至244±33 mosmol/kg H₂O（P＜0.00），但第二次注射血管升压素后，尿渗透压从106±14显著升高至702±69 mosmol/kg H₂O（P＜0.001）。在第三组研究中，检测了在给予氯苯那敏（2 mg/kg）（一种与吲哚美辛化学结构不同的前列腺素合成抑制剂）前后，相同100 - mU剂量血管升压素的抗利尿作用。第一次注射血管升压素后，尿渗透压从83±7升高至216±16 mosmol/kg H₂O（P＜0.001），第二次注射血管升压素后，尿渗透压从101±8升高至734±86 mosomol/kg H₂O（P＜0.001）。与吲哚美辛研究一样，抑制前列腺素合成后血管升压素抗利尿作用的这种增强非常显著（P＜0.001）。因此，这些结果表明前列腺素在调节哺乳动物肾脏中血管升压素的水渗透作用方面具有生理作用。
