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.
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.