Different effect of crowding stress on cardiac ischemic tolerance in borderline and spontaneously hypertensive male and female rats

Authors: Veronika Ledvenyiova 1    Iveta Bernatova 2    Peter Slezak 2    Ivan Gablovsky 1    Slavka Carnicka 1    Monika Bartekova 3    Tanya Ravingerova 1   
1 Institute for Heart Research, Slovak Academy of Sciences, Centre of Excellence SAS NOREG, Bratislava, Slovak Republic    2 Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Centre of Excellence SAS NOREG, Bratislava, Slovak Republic    3 Institute for Heart Research, Slovak Academy of Sciences, Centre of Excellence SAS NOREG, Bratislava, Slovak Republic.   
Year: 2014
Section: Cellular metabolism, physiology, molecular biology and genetics
Abstract No.: 939
ISBN: 978-80-970712-6-4

Genetic predisposition and social stress may represent important risk factors in etiology of hypertension associated with impaired myocardial response to ischemia and reperfusion (I/R) in male and female heart. Sex is an important determinant of cardiovascular morbidity and mortality in human population, where men are at higher risk than age-matched premenopausal women. The capability for activation of intrinsic tolerance to I/R injury observed in females as well as in males may persist even in the hearts of animals with genetic predisposition to hypertension and may be modified by long-lasting cardiac adaptation to stressful conditions. For this reason, we aimed to test the impact of chronic stress on the response to sustained I/R in borderline/spontaneously hypertensive rats (BHR/SHR) in comparison with its effects in normotensive Wistar Kyoto (WKY) counterparts.

Male and female 5-week-old BHR, SHR and age-matched WKY rats were exposed to 2-week crowding stress (CS), induced by caging five rats per cage in a cage for two (200 cm2/rat), while controls (non-CS) were kept four rats per cage in cages for six animals (480 cm2/rat). Langendorff-perfused hearts of stressed and non-stressed WKY, BHR and SHR animals were exposed to 30-min global ischemia and 2-h reperfusion for the evaluation of reperfusion-induced ventricular arrhythmias, recovery of contractile function and size of myocardial infarction (IS, TTC staining).

Female non-CS WKY hearts are more susceptible to more sever forms of tachyarrhythmias when compared to their normotensive male counterparts. Tolerance to reperfusion-induced ventricular arrhythmias was significantly decreased in hearts of non-stressed BHR of both sexes. Opposite effect was seen in hearts of non-CS SHRs. Interestingly, exposure to crowding stress significantly decreased the total duration of VT in BHR males and females as well as WKY females. Stressed hypertensive animals of both sexes exhibited higher susceptibility to VT. Non-CS BHR male and female hearts showed decrease in lethal injury, which was significant only in females. Oposite effect was observed in non-CS SHRs. IS was not affected by CS in WKY as well as in BHR and SHR hearts of both sexes. Exposure the rats to the mild social stressor resulted in statisticaly important decrease in NOS activity in left ventricle of BHRs as well as SHRs of both sexes. In WKY animals no change in NOS activity was seen after crowding.

Social stress modifies parameters of I/R injury in a distinct way. Inherited predisposition to hypertension may be responsible for changes in cardiac ischemic tolerance of animals exposed to social stress, which appears to be sex-dependent.

Supported by grants: APVV-0523-10, APVV-0102-11.