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.File | Dimensione | Formato | |
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