[Experimental pharmacology of the in vivo kidney: renal actions of cAMP-related drugs].
The kidney plays a pivotal role in cardiovascular homeostasis through control of extracellular fluid volume, the mechanisms of which have been studied in detail at both cellular and molecular levels in each portion of the kidney. Renal clearance experiments in vivo are useful for analyzing renal functions as the integrated system of vascular, glomerular and tubular components. Physiological responses and drug effects within the kidney can be more clearly analyzed by measuring renal release of endogenous substances and by applying intrarenal arterial drug administration. For example, our recent studies in anesthetized dogs revealed the participation of phosphodiesterase IV in regulation of renal cAMP level and the influences by changes in renal cAMP level on renal hemodynamics, glomerular filtration and tubular reabsorption. The in vivo experiments also allow us to evaluate a sequence of events in the neural control of renal functions. We observed that an adenylate cyclase activator counteracted hypofiltration to attenuate antinatriuresis during sympathetic activation without inhibiting neurotransmitter release. The experiments in the in vivo kidney, although they provide only indirect information on intracellular events, are necessary for understanding the total renal functions and could thereby contribute to physiology and pharmacology of the cardiovascular system.
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Laboratory of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000502:physiology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D004285:Dogs; D005919:Glomerular Filtration Rate; D006439:Hemodynamics; D006706:Homeostasis; D007668:Kidney / Q000378:metabolism / Q000502:physiology*; D007684:Kidney Tubules / Q000378:metabolism
D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4