title: Pretreatment with Relaxin Does Not Restore NO-Mediated Modulation of Calcium Signal in Coronary Endothelial Cells Isolated from Spontaneously Hypertensive Rats.
abstract: We demonstrated that in coronary endothelial cells (RCEs) from normotensive Wistar Kyoto rats (WKY), the hormone relaxin (RLX) increases NO production and reduces calcium transients by a NO-related mechanism. Since an impairment of the NO pathway has been described in spontaneously hypertensive rats (SHR), the present study was aimed at exploring RLX effects on RCEs from SHR, hypothesizing that RLX could restore calcium responsiveness to NO. RCEs were isolated from WKY and SHR. Calcium transients were evaluated by image analysis after the administration of angiotensin II or α-thrombin. Angiotensin II (1 µM) caused a prompt rise of [Ca2+]i in WKY and SHR RCEs and a rapid decrease, being the decay time higher in SHR than in WKY. NOS inhibition increased calcium transient in WKY, but not in SHR RCEs. Whereas RLX pretreatment (24 h, 60 ng/mL) was ineffective in SHR, it strongly reduced calcium transient in WKY in a NO-dependent way. A similar behavior was measured using 30 U/mL α-thrombin. The current study offers evidence that RLX cannot restore NO responsiveness in SHR, suggesting an accurate selection of patients eligible for RLX treatment of cardiovascular diseases.
authors.affiliation: Departments of Clinical & Experimental Medicine, Research Unit of Histology & Embryology University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. silvia.nistri@unifi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Nistri
authors.affiliation: NEUROFARBA, Section of Pharmacology & Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. lorenzo.mannelli@unifi.it.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.affiliation: NEUROFARBA, Section of Pharmacology & Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. carla.ghelardini@unifi.it.
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.affiliation: NEUROFARBA, Section of Pharmacology & Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. mattezana.mz@gmail.com.
authors.forename: Matteo
authors.initials: M
authors.lastname: Zanardelli
authors.affiliation: Departments of Clinical & Experimental Medicine, Research Unit of Histology & Embryology University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. daniele.bani@unifi.it.
authors.forename: Daniele
authors.initials: D
authors.lastname: Bani
authors.affiliation: NEUROFARBA, Section of Pharmacology & Toxicology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. paola.failli@unifi.it.
authors.forename: Paola
authors.initials: P
authors.lastname: Failli
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D008297:Male; D057054:Molecular Imaging; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012065:Relaxin / Q000378:metabolism / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology
chemical_list: D000804:Angiotensin II; D009569:Nitric Oxide; D012065:Relaxin; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013917:Thrombin; D002118:Calcium
keywords: NG-nitro-l-arginine methylester; S-nitroso-N-acetylpenicillamine; W1400; angiotensin II; cGMP-dependent protein kinase I; cardiovascular diseases; normotensive Wistar Kyoto rats; α-thrombin