Angiotensin II induces a tachyphylactic calcium response in the rabbit afferent arteriole

The influence of repeated administration of angiotensin II (AII) on smooth muscle calcium concentration ([Ca2+]i) was studied in isolated rabbit renal afferent arterioles loaded with the calcium-sensitive fluorescent probe Fura-2. [Ca2+]i was evaluated in the proximal and distal parts of the afferent arterioles. AII (10(-8) M) increased the [Ca2+]i in both these regions. A second administration of AII, however, did not elicit any response in [Ca2+]i. The response to noradrenaline administration at the end of the experiment was not affected, i.e. there was no fading or cross-desensitization. Since this desensitization was specific for AII, it was of the tachyphylaxis type. Increasing doses of AII (10(-11)-10(-8) M) did not reverse the tachyphylaxis. However, in the proximal part, pretreatment with the voltage-sensitive calcium channel blocker nifedipine (10(-6) M) blunted the tachyphylactic effect of a second administration of AII. When L-arginine (L-Arg) was administered to the bath solution, thus activating the NO system, the development of tachyphylaxis was suppressed in the proximal region. Pretreatment with the protein kinase C (PKC) inhibitor chelerythrine (10(-6) M) did not affect the tachyphylaxis. We conclude that the calcium response to AII in the isolated rabbit afferent arteriole shows tachyphylaxis. This tachyphylaxis cannot be reversed by applying increasing doses of AII (10(-11)-10(-8) M). PKC does not seem to be involved in the tachyphylactic phenomenon in this preparation. It was also found that nifedipine and NO reduced the tachyphylaxis.