title: Progression of left ventricular hypertrophy does not change the sarcoplasmic reticulum calcium store in the spontaneously hypertensive rat heart.
abstract: The spontaneously hypertensive rat (SHR) is characterized by elevated blood pressure and the development of left ventricular hypertrophy. During compensatory hypertrophy in the SHR, (26 weeks) when baseline contractile function is normal or increased, the inotropic response to beta-adrenergic stimulation is impaired. We recently showed by electron probe microanalysis (EPMA) that the amount of Ca2+ stored in the sarcoplasmic reticulum (SR) following sympathetic stimulation is not decreased in the 26-week-old SHR heart. However, with disease progression, cardiac function declines further in the SHR and the response to beta-adrenergic stimulation is more impaired. To determine whether a decreased availability of SR Ca2+ is responsible for the severely depressed inotropic response in the older SHR, we used EPMA to measure directly the amount of Ca2+ stored in the SR following activation of the beta-adrenergic pathway in papillary muscles from 76-week-old SHR and Wistar-Kyoto (WKY) controls. In order to determine if there are other alterations in ion homeostasis, we also compared elemental content of A-band and mitochondria. Papillary muscles from 76-week-old SHR and WKY were stimulated by 10 microM isoproterenol and then rapidly frozen during relaxation. The elemental content of the junctional SR. A-band and mitochondria was measured by EPMA. We observed no significant difference in SR Ca2+ content between SHR and WKY. There was also no strain-dependent difference in mitochondrial or A-band Ca2+. Overall, these results indicate that the impaired response to beta-adrenergic stimulation in the SHR at 76 weeks is not due to altered availability of SR Ca2+.
authors.affiliation: Department of Molecular Cardiology, Research Institute, Cleveland Clinic Foundation, OH 44195, USA.
authors.forename: E
authors.initials: E
authors.lastname: Keller
authors.forename: M
authors.initials: M
authors.lastname: Bond
authors.forename: C S
authors.initials: CS
authors.lastname: Moravec
mesh_terms: D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001835:Body Weight; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004577:Electron Probe Microanalysis / Q000379:methods; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008929:Mitochondria, Heart / Q000737:chemistry / Q000378:metabolism; D009119:Muscle Contraction; D009210:Myofibrils / Q000737:chemistry / Q000378:metabolism; D009929:Organ Size; D010210:Papillary Muscles / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D012519:Sarcoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000318:Adrenergic beta-Agonists; D007545:Isoproterenol; D002118:Calcium