A study in vitro of the concentrating defect associated with hypokalaemia and hypercalcaemia
The diffusional water permeabilities of collecting ducts in the presence and absence of antidiuretic hormone have been measured in isolated papillae from normal, hypokalaemic and hypercalcaemic rats. In a similar in vitro situation the effect of antidiuretic hormone on the papillary content of cyclic AMP has been measured. The diffusional water permeability of collecting ducts in the absence of antidiuretic hormone did not differ significantly in papillae taken from the different groups of rats.
The diffusional water permeability in the presence of ADH was 7.4±0.2 (S.E.M.) μm s−1 in collecting ducts taken from normal rats. In collecting ducts taken from hypokalaemic or hypercalcaemic rats the corresponding values were 5.9±0.3 and 5.8±0.5 μm s−1 respectively. This significant decrease (P<0.01) in the response to antidiuretic hormone would shift the point at which distal tubule fluid first attains isotonicity with the interstitium. If this shifts from cortex to medulla a greater amount of water enters the interstitium of the medulla and produces an impairment of maximal urinary concentrating ability and this defect could explain most of the observed results in hypokalaemic and hypercalcaemic. Cyclic AMP content of the tissue after the addition of ADH was reduced in papillae taken from hypokalaemic rats. This reduced activation of adenyl cyclase could be the mechanism responsible for the impaired response in water permeability but it is also possible that there is interference, with the chain of reactions mediating permeability changes, at a separate site.