title: A comparison of the ability of two angiotensin II receptor blocking drugs, 1-Sar; 8-Ala angiotensin II and 1-Sar, 8-Ile angiotensin II, to modify the regulation of glomerular filtration rate in the cat.
abstract: 1 Modest stimulation of the renal nerves in the anaesthetized unilaterally nephrectomized cat resulted in a 15% fall in renal blood flow, no change in glomerular filtration rate and significant falls in both the absolute and fractional rates of sodium excretion.2 The haemodynamic responses to nerve stimulation were not modified by angiotensin II blockade with 1-Sar, 8-Ala angiotensin II although the fall in absolute, but not fractional sodium excretion was significantly larger. In contrast, stimulation of renal nerves following administration of 1-Sar, 8-Ileangiotensin II caused a significant fall in glomerular filtration rate. The reductions in both absolute and fractional sodium were of the same magnitude as in the absence of drug.3 Both renal blood flow and glomerular filtration rate were autoregulated during the reduction of renal perfusion pressure and this was associated with reductions in both absolute and fractional sodium excretions.4 In the presence of 1-Sar, 8-Ala angiotensin II, the haemodynamic and sodium excretory responses to reductions in renal perfusion pressure were not significantly different from those recorded in the absence of drug. However, following administration of 1-Sar, 8-Ile angiotensin II, renal blood flow but not glomerular filtration rate, was autoregulated during reduction in renal perfusion pressure. The falls in absolute and fractional sodium excretions caused by this manoeuvre were of similar magnitude to those obtained in the absence of drug.5 The results obtained using the 1-Sar, 8-Ile angiotensin II are consistent with angiotensin II having an important intra-renal site of action to regulate glomerular filtration rate, possibly via an action at the efferent arteriole. Administration of 1-Sar, 8-Ala angiotensin II was without effect on the regulation of renal haemodynamics which it is suggested reflects a limitation in the use of this particular compound as an intrarenal angiotensin II antagonist.
mesh_terms: D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology*; D000804:Angiotensin II / Q000031:analogs & derivatives*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D004558:Electric Stimulation; D005919:Glomerular Filtration Rate / Q000187:drug effects*; D007668:Kidney / Q000502:physiology; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology*
chemical_list: D000804:Angiotensin II; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D012504:Saralasin