Sex differences to myocardial ischemia and beta-adrenergic receptor blockade in conscious rats.
We recently documented sex differences in the susceptibility to reperfusion-induced sustained ventricular tachycardia and beta-adrenergic receptor blockade in conscious rats. However, the effect of sex on ischemia-induced ventricular arrhythmias and beta-adrenergic receptor blockade is under-investigated. Therefore, we tested the hypothesis that gonadal hormones influence the ventricular arrhythmia threshold (VAT) induced by coronary artery occlusion as well as the response to beta-adrenergic receptor blockade. The VAT was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Male and female intact and gonadectomized (GnX) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, as well as a Doppler ultrasonic flow probe to measure cardiac output and a snare around the left main coronary artery. The VAT was determined in conscious rats by pulling on the snare. The VAT was significantly longer in intact females (5.56 +/- 0.19) vs. intact males (4.31 +/- 0.14 min). This sex difference was abolished by GnX. Specifically, GnX decreased the VAT in females (4.55 +/- 0.22) and increased the VAT in males (5.14 +/- 0.30 min). Thus male sex hormones increase and female sex hormones decrease the susceptibility to ischemia-induced sustained ventricular tachycardia. beta-Adrenergic receptor blockade increased the VAT in intact males and GnX females only. Thus gonadal hormones influence the response to beta-adrenergic receptor blockade. Uncovering major differences between males and females in the pathophysiology of the cardiovascular system may result in sex-specific optimization of patient treatments.
Lujan
Heidi L
HL
Wayne State Univ. School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA. hlujan@med.wayne.edu
Dicarlo
Stephen E
SE
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003243:Consciousness; D003331:Coronary Vessels / Q000601:surgery; D004195:Disease Models, Animal; D005260:Female; D012739:Gonadal Steroid Hormones / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D008026:Ligation; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009919:Orchiectomy; D010052:Ovariectomy; D051381:Rats; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism; D012107:Research Design; D012737:Sex Factors; D017180:Tachycardia, Ventricular / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D013686:Telemetry; D013997:Time Factors
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D012739:Gonadal Steroid Hormones; D018342:Receptors, Adrenergic, beta-1; D008790:Metoprolol