Mechanismof action The transport of sodium is a process that occurs in thekidney. Diuretic drugs inhibit this process specifically in the nephronfunctional unit of kidney.
Burg et al. Furosemide is a weak acid,actively secreted into the proximal convoluted tubule, and exerts its effectfrom inside of luminal surface of the ascending limb of Henle’s loop. Accordingto Hanze et al. Furosemide cause increased urinary loss ofsodium, chloride, calcium, magnesium and to a lesser extent potassium in manand these effects are independent of glomerular filtration rate. It is evidenttherefore that furosemide increases urinary loss of several ion species and isnot specific for sodium alone.
According to Aurbach et al. The renal reabsorptionof calcium is controlled by parathyroid hormone, and that this hormone acts ata cellular level through a cyclic 3′,5′-adenosine monophosphate (cAMP)dependent system.Important evidence on the renal action of furosemide hasbeen provided by Burg et al. using the thick ascending limb of Henle’sloop from rabbits. These authors have shown that active transport of chlorideis the driving force for ionic movement in this part of the nephron, thechloride being passively followed by sodium ions. This transport process is inhibited by the presence of 10-5 or 10 -6 M furosemide in the luminal fluid.
We know that the inhibition ofionic reabsorption from Henle’s loop is one of the major effects of furosemide inthe human kidney, and this has the effect of reducing concentrating ability inpatients who receive it (Anderton and Kincaid-Smith, 1971).In dogs, furosemide in large doses has been shown toinhibit sodiumreabsorption in the proximal tubule (Seldin et al., 1966),and it seemslikely that a similar phenomenon is seen in the humankidney.We have used the isolated bladder of the toad, Bufomarinus, as amodel system to investigate the cellular mode of actionof furosemide.This tissue actively transports sodium which is passivelyfollowed bychloride ions.
Sodium transports from the urine into thetransportingepithelial cells consists of two components, a passivecomponent and acarrier mediated component (Ferguson and Smith, 1972).This entrystep appears to be rate-limiting in the transepithelialflow of sodium.Sodium transport across the tissue is stimulated byvasopressin, whichincreases this rate of sodium entry into the epithelialcells. It is importantto outline the biochemical steps by which vasopressin isthoughtto increase entry of sodium.
It is unnecessary to go intoall the evidencefor and against the idea that the effects of vasopressinon sodium transportare mediated by cAMP, and the following is the generallyagreedsequence of biochemical events.