AT1 receptors mediate angiotensin II–induced release of nitric oxide in afferent arterioles
| Autor: | A. Erik G. Persson, Pontus B. Persson, Andreas Steege, En. Y. Lai, Ralf Mrowka, Andreas Patzak |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
Male
medicine.medical_specialty Afferent arterioles angiotensin II Kidney Nitric Oxide Receptor Angiotensin Type 1 Nitric oxide Mice chemistry.chemical_compound Arteriole medicine.artery Internal medicine Renin–angiotensin system medicine Animals Vasoconstrictor Agents RNA Messenger DAF-FM Receptors Angiotensin Angiotensin II receptor type 1 Dose-Response Relationship Drug biology nitric oxide synthase afferent arteriole Angiotensin II Mice Inbred C57BL Nitric oxide synthase Arterioles Endocrinology medicine.anatomical_structure glomerular hemodynamics chemistry Vasoconstriction Nephrology biology.protein cardiovascular system medicine.symptom hormones hormone substitutes and hormone antagonists isolated perfused arterioles |
| Zdroj: | Kidney International. (5):1949-1958 |
| ISSN: | 0085-2538 |
| DOI: | 10.1111/j.1523-1755.2004.00981.x |
| Popis: | AT1 receptors mediate angiotensin II–induced release of nitric oxide in afferent arterioles.BackgroundRecent studies have indicated that angiotensin II (Ang II) possibly activates the nitric oxide (NO) system. We investigated the role of AT receptor subtypes (AT-R) in mediating the Ang II–induced NO release in afferent arterioles (Af) of mice.MethodsIsolated Af of mice were perfused, and the isotonic contraction measured. Further, NO release was determined using DAF-FM, a fluorescence indicator for NO. Moreover, we qualitatively assessed the expression of AT-R at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR).ResultsAng II reduced luminal diameters dose dependently (67.3 ± 6.3% at 10−6 mol/L). Inhibition of AT2-R with PD123.319 did not change the Ang II contractile response. AT1-R blockade with ZD7155 inhibited contraction. Stimulation of AT2-R during AT1-R inhibition with ZD7155, and preconstriction with norepinephrine (NE) had no influence on the diameter. Drug application via the perfusion pipette changed flow and pressure, and enhanced NO fluorescence by ΔF = 4.0 ± 0.4% (N = 14, background). Luminal application of Ang II (10−7 mol/L) increased the NO fluorescence by ΔF = 9.9 ± 1.2% (N = 8). AT1-R blockade blunted the increase to background levels (ΔF to 4.0 ± 0.3%, N = 6, P < 0.05), but AT2-R blockade did not (8.1 ± 0.9%, N = 9). L-NAME nearly abolished the Ang II effect on the NO fluorescence (ΔF = 1.6 ± 0.5% (N = 8). NE did not increase NO release beyond the background levels. RT-PCR showed expression of both AT1-R and AT2-R.ConclusionThe results indicate an Ang II–induced NO release in Af of mice, which is mediated by AT1-R. Thus, Ang II balances its own constrictor action in Af. This control mechanism is very important in view of high renin and angiotensin II concentration in the juxtaglomerular apparatus. |
| Databáze: | OpenAIRE |
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