Angiotensin II-Induced Calcium Signalling in Isolated Glomeruli from Fish Kidney (Oncorhynchus mykiss) and Effects of Losartan

Abstract

Glomeruli were isolated from the kidney of freshwater-adapted rainbow trout,Oncorhynchus mykiss,to qualitatively evaluate changes in cellular calcium associated with angiotensin II ([Asn1Val5]-Ang II) receptor stimulation and antagonism by the Ang II receptor antagonist losartan. Microspectrofluorometry using the fluorescent calcium indicator dye Calcium Green recorded fluorescence changes in isolated single glomeruli. Isolated glomeruli containing ester-loaded Calcium Green showed an Ang-II-induced transient rise in fluorescence. This transient rise showed an increased peak amplitude with increased Ang II concentration (10−9to 10−6M), but only a very small response was detectable in glomeruli exposed to 10−9M Ang II. The biphenylimidazole compound losartan (=DuP 753), an antagonist of the mammalian AT1subtype Ang II receptor, initiated a transient agonistic rise in glomerular fluorescence at high concentration (10−5, 10−4, and 10−3M). However, the responses to 10−610−7M losartan were small or very low in each case. Losartan (10−4or 10−7M) antagonised the Ang-II-induced signalling in isolated glomeruli exposed to 10−7or 10−6M Ang II, respectively. This is the first evidence for functional AT1-like Ang II receptors coupled to cellular calcium signalling in the glomeruli of rainbow trout.