Intrarenal actions of the new adenosine agonist CGS 21680A, selective for the A2 receptor.
The purpose of this study was to define the direct intrarenal actions of the new adenosine agonist CGS 21680A (hydrochloride "A" salt of (2-[p-2-carboxyethyl)phenethylamino]5'-N-ethyl-carboxamido adenosine), which is selective for the A2 receptor. CGS 21680A was infused into the left renal artery, while simultaneously measuring blood pressure (BP) and parameters of renal function from both the left and right kidneys. At doses higher than 0.05 micrograms/kg/min, CGS 21680A appeared to leak from the circulation of the infused kidney in pharmacologically significant quantities, inasmuch as BP fell and renal blood flow was increased and renal vascular resistance decreased in the noninfused contralateral kidney. At doses of 0.025 to 0.05 micrograms/kg/min, CGS 21680A appeared localized to the renal circulation, because neither BP nor any measured parameter of contralateral renal function was altered. Intrarenal infusion of 0.025 to 0.05 micrograms/kg/min of CGS 21680A increased renal blood flow but not glomerular filtration rate leading to a fall in the filtration fraction. Urine volume and urinary sodium excretion were unaffected by selective intrarenal infusion of CGS 21680A. Plasma renin activity and renin secretion rate were also not altered significantly by intrarenal infusion of 0.05 micrograms/kg/min of CGS 21680A. In contrast plasma renin activity increased significantly in response to the intrarenal infusion of 0.075 micrograms/kg/min of CGS 21680A, a dose which leaked from the kidney and lowered BP. The results presented suggest that the new adenosine agonist CGS 21680A exerts a direct intrarenal effect on renal hemodynamics, but does not affect urine volume or sodium excretion or directly influence renin release.
Levens
N
N
Pharmaceuticals Division, Ciba-Geigy Corporation, Summit, New Jersey.
Beil
M
M
Schulz
R
R
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D007261:Infusions, Intra-Arterial; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D008297:Male; D010627:Phenethylamines / Q000494:pharmacology*; D011983:Receptors, Purinergic / Q000187:drug effects* / Q000378:metabolism; D012079:Renal Circulation / Q000502:physiology; D012083:Renin / Q000097:blood / Q000378:metabolism
D010627:Phenethylamines; D011983:Receptors, Purinergic; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D012083:Renin; D000241:Adenosine