ABSTRACT In microcoronary endothelial cells (RCEs) from spontaneously hypertensive rats (SHR), the NO/cyclic GMP-dependent proteinkinase I (cGKI) pathway cannot regulate the cytosolic calcium ([Ca2+]i) dynamic as in RCEs from Wistar Kyoto rats (WKY). We investigated the altered downstream NO target in SHR cells and, since cGKI expression was low, whether the re-expression of cGKIα in SHR RCEs could restore NO calcium responsiveness. We measured [Ca2+]i dynamic by fura2 imaging analysis and cGKI level by RT-PCR and WB in SHR and WKY RCEs. Plasmids encoding for enhanced green fluorescence protein (EGFP) or cGKIα-EGFP were transiently transfected in SHR RCEs and [Ca2+]i was evaluated. Angiotensin-II (AT-II) increased [Ca2+]i in a concentration-dependent way in both strains. Whereas in WKY, endogenously produced NO and cyclic GMP analog decreased AT-II-induced [Ca2+]i transient, they were ineffective in SHR RCEs. The cGKI level was low in SHR cells. However, after cGKIα re-expression, endogenous NO decreased AT-II-induced [Ca2+]i transient, while eNOS and cGKI inhibition prevented it. The cGKI low expression in SHR accounts for the absent regulation of agonist-induced [Ca2+]i transient by NO/cyclic GMP pathway. Studies on cGKI in humans could contribute to a better understanding of cardiovascular pathologies.

Restoring nitric oxide cytosolic calcium regulation by cyclic GMP protein kinase Ialpha transfection in coronary endothelial cells of spontaneously hypertensive rats / Nistri S; Di Cesare Mannelli L; Mazzetti L; Feil R; Bani D; Failli P. - In: JOURNAL OF VASCULAR RESEARCH. - ISSN 1018-1172. - ELETTRONICO. - 49:(2012), pp. 221-230.

Restoring nitric oxide cytosolic calcium regulation by cyclic GMP protein kinase Ialpha transfection in coronary endothelial cells of spontaneously hypertensive rats

NISTRI, SILVIA;DI CESARE MANNELLI, LORENZO;BANI, DANIELE;FAILLI, PAOLA
2012

Abstract

ABSTRACT In microcoronary endothelial cells (RCEs) from spontaneously hypertensive rats (SHR), the NO/cyclic GMP-dependent proteinkinase I (cGKI) pathway cannot regulate the cytosolic calcium ([Ca2+]i) dynamic as in RCEs from Wistar Kyoto rats (WKY). We investigated the altered downstream NO target in SHR cells and, since cGKI expression was low, whether the re-expression of cGKIα in SHR RCEs could restore NO calcium responsiveness. We measured [Ca2+]i dynamic by fura2 imaging analysis and cGKI level by RT-PCR and WB in SHR and WKY RCEs. Plasmids encoding for enhanced green fluorescence protein (EGFP) or cGKIα-EGFP were transiently transfected in SHR RCEs and [Ca2+]i was evaluated. Angiotensin-II (AT-II) increased [Ca2+]i in a concentration-dependent way in both strains. Whereas in WKY, endogenously produced NO and cyclic GMP analog decreased AT-II-induced [Ca2+]i transient, they were ineffective in SHR RCEs. The cGKI level was low in SHR cells. However, after cGKIα re-expression, endogenous NO decreased AT-II-induced [Ca2+]i transient, while eNOS and cGKI inhibition prevented it. The cGKI low expression in SHR accounts for the absent regulation of agonist-induced [Ca2+]i transient by NO/cyclic GMP pathway. Studies on cGKI in humans could contribute to a better understanding of cardiovascular pathologies.
2012
49
221
230
Nistri S; Di Cesare Mannelli L; Mazzetti L; Feil R; Bani D; Failli P
File in questo prodotto:
File Dimensione Formato  
Nistri- JVR.pdf

Accesso chiuso

Descrizione: Full Text
Tipologia: Pdf editoriale (Version of record)
Licenza: Tutti i diritti riservati
Dimensione 491.96 kB
Formato Adobe PDF
491.96 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/638311
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact