title: Hypothyroidism: age-related influence on cardiovascular nitric oxide system in rats.
abstract: This study investigates whether changes in nitric oxide (NO) production participate in the cardiovascular manifestations of hypothyroidism and whether these changes are age-related. Sprague-Dawley rats aged 2 and 18 months old were treated with 0.02% methimazole (wt/vol) during 28 days. Left ventricular function was evaluated by echocardiography. Measurements of arterial blood pressure, heart rate, nitric oxide synthase (NOS) activity and NOS/caveolin-1 and -3 protein levels were performed. Hypothyroidism enhanced the age-related changes in heart function. Hypothyroid state decreased atrial NOS activity in both young and adult rats, associated with a reduction in protein levels of the three NOS isoforms in young animals and increased caveolin (cav) 1 expression in adult rats. Ventricle and aorta NOS activity increased in young and adult hypothyroid animals. In ventricle, changes in NOS activity were accompanied by an increase in inducible NOS isoform in young rats and by an increase in caveolins expression in adult rats. Greater aorta NOS activity level in young and in adult Hypo rats would derive from the inducible and the endothelial NOS isoform, respectively. Thyroid hormones would be one of the factors involved in the modulation of cardiovascular NO production and caveolin-1 and -3 tissue-specific abundance, regardless of age. Hypothyroidism appears to contribute in a differential way to aging-induced changes in the myocardium and aorta tissues. Low thyroid hormones levels would enhance the aging effect on the heart. Age-related changes in NO production participate in the cardiovascular manifestations of hypothyroidism.
authors.affiliation: Department of Physiology, School of Pharmacy and Biochemistry, Universidad de Buenos Aires, Buenos Aires, Argentina, IQUIMEFA-CONICET. ivonnesarati@conicet.gov.ar
authors.forename: Lorena I
authors.initials: LI
authors.lastname: Sarati
authors.forename: Carla R
authors.initials: CR
authors.lastname: Martinez
authors.forename: Nicolás
authors.initials: N
authors.lastname: Artés
authors.forename: Noelia
authors.initials: N
authors.lastname: Arreche
authors.forename: Juan J
authors.initials: JJ
authors.lastname: López-Costa
authors.forename: Ana M
authors.initials: AM
authors.lastname: Balaszczuk
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Fellet
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D013956:Antithyroid Agents; D001808:Blood Vessels / Q000378:metabolism*; D015153:Blotting, Western; D051242:Caveolin 1 / Q000378:metabolism*; D007037:Hypothyroidism / Q000139:chemically induced / Q000150:complications / Q000378:metabolism*; D008297:Male; D008713:Methimazole; D009206:Myocardium / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D013956:Antithyroid Agents; C495537:Cav1 protein, rat; D051242:Caveolin 1; D013963:Thyroid Hormones; D009569:Nitric Oxide; D008713:Methimazole; D019001:Nitric Oxide Synthase