| [PMID]: | 28137984 |
| [Au] Autor: | Jackson EK; Zhang Y; Cheng D |
| [Ad] Endereço: | From the Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, PA. edj@pitt.edu. |
| [Ti] Título: | Alkaline Phosphatase Inhibitors Attenuate Renovascular Responses to Norepinephrine. |
| [So] Source: | Hypertension;69(3):484-493, 2017 Mar. |
| [Is] ISSN: | 1524-4563 |
| [Cp] País de publicação: | United States |
| [La] Idioma: | eng |
| [Ab] Resumo: | Tissue nonspecific alkaline phosphatase (TNAP) contributes to the production of adenosine by the kidney, and A -receptor activation enhances renovascular responses to norepinephrine. Therefore, we hypothesized that TNAP regulates renovascular responsiveness to norepinephrine. In isolated, perfused rat kidneys, the TNAP inhibitor l-p-bromotetramisole (0.1 mmol/L) decreased renal venous levels of 5'-AMP (adenosine precursor) and adenosine by 61% ( <0.0384) and 62% ( =0.0013), respectively, at 1 hour into treatment and caused a 10-fold rightward shift of the concentration-response relationship to exogenous norepinephrine ( <0.0001). Similarly, 2 other TNAP inhibitors, levamisole (1 mmol/L) and 2,5-dimethoxy-N-(quinolin-3-yl)benzenesulfonamide (0.02 mmol/L), also right shifted the concentration-response relationship to norepinephrine. The ability of TNAP inhibition to blunt renovascular responses to norepinephrine was mostly prevented or reversed by restoring A -adenosinergic tone with the A -receptor agonist 2-chloro-N -cyclopentyladenosine (100 nmol/L). All 3 TNAP inhibitors also attenuated renovascular responses to renal sympathetic nerve stimulation, suggesting that TNAP inhibition attenuates renovascular responses to endogenous norepinephrine. In control propranolol-pretreated rats, acute infusions of norepinephrine (10 µg/kg/min) increased mean arterial blood pressure from 95±5 mm Hg to a peak of 169±4 mm Hg and renovascular resistance from 12±2 mm Hg/mL/min to a peak of 55±12 mm Hg/mL/min; however, in rats also treated with intravenous l-p-bromotetramisole (30 mg/kg), the pressor and renovascular effects of norepinephrine were significantly attenuated (blood pressure: basal and peak, 93±7 and 146±6 mm Hg, respectively; renovascular resistance: basal and peak, 13±2 and 29±5 mm Hg/mL/min, respectively). TNAP inhibitors attenuate renovascular and blood pressure responses to norepinephrine, suggesting that TNAP participates in the regulation of renal function and blood pressure. |
| [Mh] Termos MeSH primário: |
Fosfatase Alcalina/antagonistas & inibidores
Pressão Sanguínea/efeitos dos fármacos
Levamisol/farmacologia
Norepinefrina/farmacologia
Artéria Renal/efeitos dos fármacos
Circulação Renal/efeitos dos fármacos
Sistema Nervoso Simpático/efeitos dos fármacos
|
| [Mh] Termos MeSH secundário: |
Animais
Rim/irrigação sanguínea
Rim/inervação
Masculino
Modelos Animais
Ratos
Ratos Sprague-Dawley
Circulação Renal/fisiologia
Resistência Vascular
|
| [Pt] Tipo de publicação: | JOURNAL ARTICLE |
[Nm] Nome de substância:
| 2880D3468G (Levamisole); EC 3.1.3.1 (Alkaline Phosphatase); X4W3ENH1CV (Norepinephrine) |
| [Em] Mês de entrada: | 1708 |
| [Cu] Atualização por classe: | 170809 |
[Lr] Data última revisão:
| 170809 |
| [Sb] Subgrupo de revista: | IM |
| [Da] Data de entrada para processamento: | 170201 |
| [St] Status: | MEDLINE |
| [do] DOI: | 10.1161/HYPERTENSIONAHA.116.08623 |
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