RESUMEN
The extracellular calcium-sensing receptor CaSR is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative [wild-type (WT)] and Cre-positive (SM22α)CaSR(Δflox/Δflox) [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca(2+)) concentrations (1-5 mM) evoked contraction in WT but only relaxation in KO aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either nitric oxide-synthase inhibition with nitro-l-arginine methyl ester or by a high-salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia, and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca(2+) concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.
Asunto(s)
Presión Sanguínea , Señalización del Calcio , Calcio/metabolismo , Hipotensión/metabolismo , Músculo Liso Vascular/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Vasoconstricción , Vasodilatación , Animales , Aorta/metabolismo , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/genética , Bradicardia/genética , Bradicardia/metabolismo , Bradicardia/fisiopatología , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/genética , Relación Dosis-Respuesta a Droga , Predisposición Genética a la Enfermedad , Frecuencia Cardíaca , Hipotensión/genética , Hipotensión/fisiopatología , Arterias Mesentéricas/metabolismo , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Músculo Liso Vascular/efectos de los fármacos , Músculo Liso Vascular/fisiopatología , Miocitos Cardíacos/metabolismo , Fenotipo , Receptores Sensibles al Calcio , Receptores Acoplados a Proteínas G/deficiencia , Receptores Acoplados a Proteínas G/genética , Vasoconstricción/efectos de los fármacos , Vasoconstricción/genética , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatación/genética , Vasodilatadores/farmacología , Remodelación VentricularRESUMEN
Suberin in extractive-free potato periderm amounts to approximately 25% determined by NaOCH(3) methanolysis. Monomeric composition is characterized by glycerol (20% of monomers), long-chain alpha, omega-diacids, omega-hydroxyacids, alkanoic acids, and alkan-1-ols, with predominance of octadec-9-enodioic acid and 18-hydroxyoctadec-9-enoic acid (39 and 15% of long-chain monomers, respectively). Aromatic hydroxycinnamyl monomers were also present (<1%). Partial depolymerization of potato periderm suberin using a Ca(OH)(2)-catalyzed methanolysis solubilized approximately 10% of suberin aliphatics. GC-MS analysis showed the presence of monomers, dimers, and trimers (87, 12, and 1% of identified compounds, respectively). A total of 26 dimers were identified by EIMS: monoacylglyceryl esters of alpha,omega-diacids, omega-hydroxyacids, and alkanoic acids (with predominance of the 1- and 2-isomers of the monoacylglyceryl ester of the octadec-9-enodioic acid), as well as feruloyl esters of omega-hydroxyacids and alkan-1-ols and a small quantity of a monoferuloylglycerol. Following a discussion of suberin macromolecular structure, it is proposed that in suberized cell walls, the polyaliphatic polymers have a three-dimensional development ensured by glycerol and exist independently from the associated polyaromatics.
Asunto(s)
Ácidos Carboxílicos/análisis , Lípidos de la Membrana/química , Solanum tuberosum/química , Ácidos Cumáricos/análisis , Dimerización , Cromatografía de Gases y Espectrometría de Masas , Glicerol/análisis , Hidroxiácidos/análisis , Lípidos , Lípidos de la Membrana/aislamiento & purificación , Espectrometría de Masa de Ion SecundarioRESUMEN
Scilla maderensis Menezes (Hyacinthaceae) is endemic to the Portuguese Archipelago of Madeira. The taxonomic proximity between Scilla L. and Urginea Steinh. genus, and also the knowledge that bulbs of Urginea maritima (L.) Baker (Scilla maritima L.) contain cardiac glycosides of the bufadienolide type, led us to a phytochemical and pharmacological study of S. maderensis. Extracts obtained from the bulbs were screened by TLC and tested in the isolated frog heart preparation. The TLC screening revealed spots with colours and R(f) values similar to those obtained for proscillaridin and scillaren A. In the frog heart preparation the extracts showed a positive inotropic effect and toxic doses induced the arrest of the heartbeat in systole. We can conclude that the bulbs of S. maderensis contain substances exerting pharmacological effects on the heart.