Sex-Specific Effects of Adrenergic-Induced Left Ventricular Remodeling in Spontaneously Hypertensive Rats.
OBJECTIVE
The aim of this work was to determine whether adrenergic-induced left ventricular (LV) dilation and eccentric remodeling in pressure-overload hypertrophy is sex specific.


RESULTS
Chronic β-adrenoreceptor activation was produced in male and female spontaneously hypertensive rats (SHRs) by means of daily administration of isoproterenol (ISO; 0.04 mg/kg daily) from 9 to 15 months of age. LV chamber dimensions were determined in vivo by means of echocardiography and ex vivo in isolated perfused heart preparations. The acute hemodynamic response to ISO, the degree of myocardial necrosis and apoptosis, and collagen distribution were also assessed. Female SHRs demonstrated inotropic and chronotropic responses to ISO similarly to male SHRs. Compared with control subjects (saline solution vehicle), following chronic ISO administration, LV end-diastolic diameter (mm) was increased in male (ISO 7.8 ± 0.3 vs control 6.6 ± 0.2; P < .001) but not in female (ISO 6.3 ± 0.2 vs control 6.2 ± 0.2; P = .23) SHRs. Similarly, compared with control, ISO administration increased the volume intercept of the LV end-diastolic pressure-volume relation (mL) in male (ISO 0.31 ± 0.02 vs control 0.22 ± 0.01; P < .0001) but not in female (ISO 0.17 ± 0.01 vs control 0.17 ± 0.01; P = 1.00) SHRs. Relative wall thickness was also decreased in male SHRs receiving ISO but not in female SHRs receiving ISO. Chronic ISO administration increased the percentage of area covered by interstitial collagen in male but not in female SHRs. Finally, chronic adrenergic stimulation failed to influence LV chamber or myocardial systolic function in either male or female SHRs.


CONCLUSIONS
Male SHRs are more susceptible to adrenergic-induced LV dilation and eccentric LV remodeling than female SHRs. These effects are associated with increased collagen deposition. In pressure-overload hypertrophy, LV dilation and eccentric LV remodeling occur before LV dysfunction in male rats.
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. Electronic address: frederic.michel@wits.ac.za.
Frederic S
FS
Michel
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Mhlengi
M
Magubane
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Lebogang
L
Mokotedi
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Gavin R
GR
Norton
Cardiovascular Pathophysiology and Genomics Research Unit, School of Physiology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Angela J
AJ
Woodiwiss
D018663:Adrenergic Agents; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR; D012680:Sensitivity and Specificity; D012737:Sex Factors; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000503:physiopathology*; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D018663:Adrenergic Agents; D007545:Isoproterenol
LV dilation; adrenergic stimulation; eccentric LV remodeling; sex