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 I-Sar, 8-Ala angiotensin IT, 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 I-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 I-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.

Effect of Converting Enzyme Inhibition on the Renal Haemodynamic Responses to Noradrenaline Infusion in the Rat

“…Thus the ability to maintain glomerular filtra-0007-1188/82/030553-06 $01.00 tion rate at control values during renal nerve stimulation was impaired following inhibition of the reninangiotensin system (Johns, Lewis & Singer, 1976;Johns, 1979;1980). Such an effect was consistent with the suggestion of locally generated angiotensin II having a preferential site of action at the efferent arteriole.…”

“…Brunner & Gavras, 1981). In spite of this reservation in the use of converting enzyme inhibitors, we chose to use teprotide as a previous study had shown that the effectiveness of angiotensin II receptor blocking drugs at intrarenal sites was very variable (Johns, 1980). The dose of teprotide used in the present study completely blocked the increases in blood pressure caused by moderate doses of angiotensin I and was similar to that used in acute studies by Thurston & Swales (1978) and by ourselves in the cat (Johns, 1979).…”

“…Brunner & Gavras, 1981). In spite of this reservation in the use of converting enzyme inhibitors, we chose to use teprotide as a previous study had shown that the effectiveness of angiotensin II receptor blocking drugs at intrarenal sites was very variable (Johns, 1980).…”

“…Studies by Hall and co-workers using the anaesthetized dog and the experimental manoeuvre of reduction in renal perfusion pressure over the autoregulatory range and of ourselves, using direct electrical stimulation of the renal nerves in the cat, have shown that the ability to regulate glomerular filtration rate is reduced following suppression of the renin-angiotensin system with high salt and DOCA (Hall, Guyton & Cowley, 1977), or blockade of neural renin release with a P-adrenoceptor antagonist (Johns et al, 1976), administration of the receptor blocking drug 1-Sar, 8-Ile, angiotensin II (Hall, Guyton, Jackson, Coleman, Lohmeirer & Trippodo, 1977;Johns, 1980) or following inhibition of converting enzyme (Hall, Coleman, Guyton, Balfe & Salgado, 1979;Johns, 1979). As yet, evidence of such a role for intrarenal angiotensin II in the rat is indirect.…”

Renal Autoregulatory Efficiency during Angiotensin-Converting Enzyme Inhibition in Dogs on a Low Sodium Diet

“…Some studies have observed au toregulation o f G F R along with R B F follow ing blockade o f the renin-angiotensin system [5,8,9,14]. Other studies have indicated that there is an uncoupling in antoregulation of G F R and R BF during inhibition of the renin-angiotensin system [11,13,15].…”