Effects of Hydrochlorothiazide on the Renal Cyclic Nucleotides Level

Hydrochlorothiazide가 신장의 Cyclic Nucleotides 함량에 미치는 영향

To determine the relationship between hydrochlorothiazide-induced diuretic action and cyclic nucleotides, the effects of hydrochlorothiazide (5 mg/kg, i.v.) on the renal tissue level of cyclic nucleotides and the renal adenylate cyclase and guanylate cyclase activity were investigated. Hydrochlorothiazide elecitied the maximal diuretic effect between 10 and 20 min after the injection of drug. The increased urine flow and urinary electrolytes excretion returned to the control levels 60 min after the injection of drug. 5 and 15 min after drug administration the cAMP level of renal tissue was significantly decreased, but 60 min after the cAMP level was not different from the control level. The cGMP level of renal tissue was not affected by hydrocholorothiazide. Hydrochlorothiazide $(5\;{\times};10^{-4}\;M)$ inhibited the renal adenylate cyclase but not affected the renal guanylate cyclase. These results suggest that cAMP may be involved in the renal action mechanism of hydrochlorothiazide and the involvement of cGMP is uncertain.

hydrochlorothiazide의 이뇨작용과 cyclic nucleotides와의 관계를 알아보기 위해 신조직내cyclic nucleotides 함량과 adenylate cyclase 및 guanylate cyclase 활성에 대한 hydrochlorothiazide의 영향을 관찰하였다. hydrochlorothiazide를 정맥내 투여시 약물투여 후 10분과 20분 사이에서 이뇨작용이 가장 강하게 나타났으며 60분 경과시는 이뇨작용이 소실되었다. 신조직 내 CAMP 함량은 약물투여 후 5분과 15분에 유의하게 감소되었으며 60분 경과시는 대조군과 차이가 없었다. 신조직내 cGMP 함량은 hydrochlorothiazide에 의해 영향받지 않았다. 신조직의 adenylate cyclase는 hydrochlorothiazide에 의해 활성이 억제되었으며 guanylate cyclase는 영향받지 않았다. 이상의 결과는 hydrochlorothiazide의 이뇨작용에 cAMP가 어떤 관련성을 가질 것을 시사하며 cGMP는 관련성이 없는 것으로 사료된다.