Angiotensin II enhances the afferent arteriolar response to adenosine through increases in cytosolic calcium
2009 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 196, no 4, 435-445 p.Article in journal (Refereed) Published
Aims: Angiotensin II (Ang II) is a strong renal vasoconstrictor and modulates the tubuloglomerular feedback (TGF). We hypothesized that Ang II at low concentrations enhances the vasoconstrictor effect of adenosine (Ado), the mediator of TGF. Methods: Afferent arterioles of mice were isolated and perfused, and both isotonic contractions and cytosolic calcium transients were measured. Results: Bolus application of Ang II (10(-12) and 10(-10)M) induced negligible vasoconstrictions, while Ang II at 10(-8) M reduced diameters by 35%. Ang II at 10(-12), 10(-10), and 10(-8) M clearly enhanced the arteriolar response to cumulative applications of Ado (10(-11) to 10(-4)M). Ado application increased the cytosolic calcium concentrations in the vascular smooth muscle, which were higher at 10(-5)M than at 10(-8)M. Ang II (10(-11) to 10(-6)M) also induced concentration-dependent calcium transients, which were attenuated by AT(1) receptor inhibition. Simultaneously applied Ang II (10(-10)M) additively enhanced the calcium transients induced by 10(-8) and 10(-5) M Ado. The transients were partly inhibited by AT(1) or A(1) receptor antagonists, but not significantly by A(2) receptor antagonists. Conclusion: A low dose of Ang II enhances Ado-induced constrictions, partly via AT(1) receptor-mediated calcium increase. Ado increases intracellular calcium by acting on A(1) but not A(2) receptors. The potentiating effect of Ang II on Ado-induced arteriolar vasoconstrictions may involve calcium sensitization of the contractile machinery, as Ang II only additively increased cytosolic calcium concentrations, while its effect on the arteriolar constriction was more than additive. The potentiating effect of Ang II might contribute to the resetting of TGF.
Place, publisher, year, edition, pages
2009. Vol. 196, no 4, 435-445 p.
renal arterioles, tubuloglomerular feedback, vascular smooth muscle
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-104349DOI: 10.1111/j.1748-1716.2009.01956.xISI: 000267948300009PubMedID: 19141138OAI: oai:DiVA.org:uu-104349DiVA: diva2:219672