Blonde L, Wehmann R E, Steiner A L
J Clin Invest. 1974 Jan;53(1):163-72. doi: 10.1172/JCI107534.
Previously, in an attempt to understand the mechanisms involved in the regulation of plasma cyclic nucleotides, we measured concentrations of adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) in plasma from selected blood vessels of anesthetized dogs. The observation that the renal venous plasma concentrations of both cyclic nucleotides were less than arterial concentrations suggested that the kidney might be an important site for the elimination of these compounds from plasma and prompted further investigation of the renal handling of these compounds. Tracer doses of either [(3)H]cAMP or [(3)H]cGMP were administered to anesthetized dogs by constant intravenous infusion, and metabolic clearance rates were determined. Concentrations of endogenous cyclic nucleotide and of cyclic nucleotide radioactivity were measured in aortic and renal venous plasma as well as in urine. Renal venous plasma [(3)H]cGMP was 39% and [(3)H]cAMP was 65% of the concentration in arterial plasma. Endogenous cyclic nucleotide levels showed a similar relationship. The plasma clearance rates (PCR) were 271+/-27 ml/min (mean+/-SE) for cGMP and 261+/-17 for cAMP. The total kidney clearance (calculated as the renal plasma flow x renal cyclic nucleotide extraction ratio) accounted for 52+/-4% and 30+/-2% of the PCR for cGMP and cAMP, respectively. Only about two-thirds of the total kidney clearance of each cyclic nucleotide could be accounted for by urinary excretion, the remainder presumably being the result of renal metabolism. The urinary clearances of (3)H-labeled cGMP (40.9+/-4.2 ml/min) and endogenous cGMP (45.0+/-2.3 ml/min) were not significantly different from each other. Both were approximately 50% greater than the glomerular filtration rate, which was 27.1+/-2.0 ml/min, indicating that a significant amount of urinary cGMP is derived from plasma by tubular secretion. In contrast, the urinary clearances of (3)H-labeled cAMP (23.7+/-1.9 ml/min) and endogenous cAMP (27.2+/-2.6 ml/min) were nearly equal both to each other and to the glomerular filtration rate, which was 24.6+/-1.7 ml/min. Thus, in the dog, glomerular filtration of plasma cAMP appears to be responsible for most of the cAMP found in urine. Renla production of cAMP, which in humans contributes from a third to a half of the urinary cAMP, was quantitatively of minor importance in the dog.Thus, under the conditions of these experiments in dogs, renal elimination appears to be responsible for half of the PCR of cGMP and about a third of the PCR of cAMP. About a third of the renal elimination of both cyclic nucleotides appears to be due to metabolic degradation within the kidney, and the balance is due to excretion in the urine.
此前，为了试图理解参与调节血浆环核苷酸的机制，我们测定了麻醉犬选定血管血浆中3',5'-环磷酸腺苷（cAMP）和3',5'-环磷酸鸟苷（cGMP）的浓度。观察到两种环核苷酸的肾静脉血浆浓度均低于动脉浓度，这表明肾脏可能是血浆中这些化合物清除的重要部位，并促使我们进一步研究肾脏对这些化合物的处理。通过持续静脉输注向麻醉犬给予示踪剂量的[(3)H]cAMP或[(3)H]cGMP，并测定代谢清除率。测定主动脉和肾静脉血浆以及尿液中内源性环核苷酸和环核苷酸放射性的浓度。肾静脉血浆[(3)H]cGMP为动脉血浆浓度的39%，[(3)H]cAMP为65%。内源性环核苷酸水平呈现类似关系。cGMP的血浆清除率（PCR）为271±27 ml/min（均值±标准误），cAMP为261±17。肾脏总清除率（按肾血浆流量×肾环核苷酸提取率计算）分别占cGMP和cAMP的PCR的52±4%和30±2%。每种环核苷酸肾脏总清除率中只有约三分之二可由尿排泄解释，其余可能是肾脏代谢的结果。(3)H标记的cGMP（40.9±4.2 ml/min）和内源性cGMP（45.0±2.3 ml/min）的尿清除率彼此无显著差异。两者均比肾小球滤过率约高50%，肾小球滤过率为27.1±2.0 ml/min，这表明尿中大量的cGMP是由肾小管分泌从血浆而来。相比之下，(3)H标记的cAMP（23.7±1.9 ml/min）和内源性cAMP（27.2±2.6 ml/min）的尿清除率彼此相近且与肾小球滤过率相近，肾小球滤过率为24.6±1.7 ml/min。因此，在犬中，血浆cAMP的肾小球滤过似乎是尿中大部分cAMP的来源。在人类中，肾脏产生的cAMP占尿中cAMP的三分之一到一半，而在犬中其数量上不太重要。因此，在犬的这些实验条件下，肾脏清除似乎占cGMP的PCR的一半以及cAMP的PCR的约三分之一。两种环核苷酸约三分之一的肾脏清除似乎是由于肾脏内的代谢降解，其余是由于尿排泄。
