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Rats were prepared with chronic cannulae in the carotid artery, jugular vein and urinary bladder; they were then kept 2 days to allow recovery from surgery. A steady-state continuous saline diuresis was established, then various anaesthetic agents were injected and changes in the urine flow, sodium and potassium excretion rates, GFR, ERPF, ERBF and blood pressure were measured. Five groups of rats were studied: (1) control animals given saline in place of any anaesthetic agent, all parameters measured remained constant; (2) althesin (1.2 mg/kg), all parameters remained constant except for the blood pressure which decreased slightly for 5 min; (3) althesin (12 mg/kg); (4) ketamine (50 mg/kg); (5) pentothal (50 mg/kg). The above anaesthetics altered all of the measured parameters except urine output. Various mechanisms for these anaesthetic agents are discussed. In althesin anaesthetized rats, all the retarded renal parameters recovered within 30 min. It is concluded that for the study of renal function, if a brief anaesthesia is needed, althesin is a more suitable anaesthetic agent.

Dopamine and isoprenaline have been examined for their effects on guinea-pig renal blood flow in vivo and on cAMP production in a mainly isolated glomeruli/blood vessel preparation in vitro. The renal vasodilatation caused by both of these drugs can be differentiated by the use of specific antagonists, sulpiride blocking the effects of dopamine, and propranolol the vasodilatation produced by isoprenaline. Similarly, both drugs stimulated cAMP production, isoprenaline being much more active than dopamine (1000X) in this respect. Again, the dopamine antagonist fluphenazine specifically inhibited the dopamine-induced cAMP increases whilst the beta blocker atenolol blocked the rise in cAMP due to isoprenaline but not that due to dopamine. Sulpiride although potently inhibiting dopamine-induced renal vasodilatation was without effect on dopamine-stimulated cAMP levels. This result is similar to that reported in the CNS where sulpiride blocks dopamine activity in a variety of tests but is without effect on the dopamine-stimulated adenylate cyclase. Two dopamine agonists, ADTN and SKF 38393 were tested, and in both preparations had potent dopaminergic activity although SKF 38393 exhibited characteristics of a partial agonist on the adenylate cyclase model.

1. Blood flow was measured in the renal cortex and medulla of anaesthetized rats by the hydrogen washout method. The effects of dopamine infusion were measured. 2. Low doses of dopamine (20 and 65 n-mole.kg-1.min-1) caused only small increases in renal blood flow, and a higher dose (200 n-mole.kg-1.min-1) caused vasoconstriction. After alpha-blockade with phenoxybenzamine (9 mumole.kg-1), all doses of dopamine caused vasodilatation in the cortex and medulla of the kidney. 3. This dopamine-induced renal vasodilatation was almost abolished by sulpiride (0.7 mumole.kg-1.min-1), but was only slightly attenuated by propranolol (10 mumole.kg-1). 4. Sulpiride did not significantly alter the renal blood flow responses to noradrenaline or isoprenaline, or the blood pressure responses to histamine, acetylcholine, 5HT, noradrenaline and isoprenaline. 5. In normal rats, infusion of sulpiride generally caused a reduction in renal cortical blood flow. This response showed a positive correlation with the initial blood pressure. 6. It is concluded that there are specific dopamine receptors in the renal vasculature of the rat, and that dopamine may play a role in the normal control of renal blood flow.

Grass carp bile, sometimes eaten by Chinese people, has previously been shown to induce acute renal failure in man and to result in the death of experimental mice and rats. A toxic extract from the bile acid fraction of grass carp bile (LD50 109 mg/kg) was injected into pentobarbitone anesthetized rats and an increase in urinary excretion of water and salts was produced. The bile extract also caused a prompt fall in systemic arterial blood pressure and cardiac output. It was also found, in vitro, that the bile salts caused a potent hemolysis. The hypothesis that hemoglobin is released from hemolysed red blood corpuscles and might be responsible for the long term renal functional damage is considered. Another alternative hypothesis is that the hypotension induced by the bile toxin may result in renal underperfusion and thus make the kidney more susceptible to the nephrotoxic action of the grass carp bile.

1. Renal function was measured in seven normo thermic (38 degrees C) and seven hypothermic (27 degrees C) dogs. 2. The glomerular filtration rate was 60 per cent lower in the hypothermic animals, and the renal blood flow as 51 per cent lower. The intrarenal distribution of blood flow was measured by the uptake of 86Rb from the blood into different regions of the kidney. Hypothermia reduced flow by 34 per cent in the outer cortex, 72 per cent in the inner cortex, 61 per cent in the outer medulla and 69 per cent in the inner medulla. 3. Radioautography indicated a high blood flow to an area of the outer medulla of hypothermic kidneys, which may indicate medullary blood flow "shunting". 4. The results have been discussed in relation to a number of clinical and experimental observations.

1 Specific high affinity binding sites for [125I]-angiotensin II have been identified in crude basolateral and brush border membranes from rat cortex. 2 A central high affinity site, KD 0.62 nM; Bmax 299 fmol/mg was identified as part of a complex multicomponent binding system. 3 This high affinity site was saturable and exhibited specificity for angiotensin II analogues and closely related peptides but not for bradykinin, substance P or peptide fragments of angiotensin II. 4 Specific [125I]-angiotensin II binding was partially dependent on NaCl. Absence of NaCl resulted in a decrease in Bmax, had no effect on the rate of association but increased the rate of dissociation of [125I]-angiotensin from its binding site.

1. Dogs cooled to 27 degrees C were compared with control dogs maintained at 38 degrees C. The mean arterial blood pressure, renal blood flow and glomerular filtration rate were lower in the hypothermic animals. 2. The relation between mean arterial blood pressure and renal blood flow was investigated. Auto-regulation of renal blood flow occurred in the kidneys of normothermic and hypothermic animals. Thus the reduction in renal blood flow during hypothermia is not due simply to the fall in mean arterial blood pressure. 3. Similarities between recordings of renal blood flow obtained at 38 degrees C and 27 degrees C suggest that its autoregulation occurs by the same mechanism at the two temperatures. 4. Autoregulation of renal blood flow occurred in hypothermic kidneys in the presence of a cold-induced vasoconstriction. The observed responses to cold and to alterations in mean arterial blood pressure may take place in different areas of the renal vasculature.

1. A study has been made of the effect of angiotensin (10(-12) g/ml.) on active and passive transport of sodium, potassium and water between rat kidney cortex slices and the incubation medium.2. Angiotensin has no effect on the passive uptake of sodium and loss of potassium by slices incubated under conditions which inhibit active transport.3. Active sodium extrusion by slices incubated under aerobic conditions is stimulated, whereas active potassium uptake is inhibited by angiotensin.4. Sodium pump activity is stimulated by angiotensin in the presence of ouabain or in the absence of potassium in the incubation medium, conditions which block the sodium for potassium exchange pump.5. There is a 2 min latent period following the application of angiotensin before a response is observed.6. These findings are discussed in relation to the mechanism of action of angiotensin on kidney sodium and fluid transport processes.

1. A study has been made of the effects of cyclic AMP, phosphodiesterase inhibitors and protein synthesis inhibitors on the response of rat kidney cortex slices to physiological doses of angiotensin.2. The additions of cyclic AMP, dibutyryl cyclic AMP and/or phosphodiesterase inhibitors to the incubation medium (conditions which would be expected to increase intracellular cyclic AMP levels) were without effect on sodium or potassium transport by kidney slices.3. Actinomycin D (an inhibitor of the transcription stage of protein synthesis), at concentrations which inhibit RNA synthesis by 75%, has no effect on either control or angiotensin stimulated sodium transport.4. Cycloheximide or puromycin (inhibitors of the translation stage of protein synthesis), at concentrations which inhibit protein synthesis by 70-80%, have no effect on control sodium and potassium transport by kidney slices, but completely block the angiotensin stimulation of these processes.5. These findings are discussed in relation to the possible involvement of cyclic AMP and protein synthesis in the mechanism of action of angiotensin on kidney sodium and potassium transport.