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The effect of age on presynaptic alpha 2 adrenoceptor-mediated regulation of norepinephrine (NE) release was studied in hearts isolated from male Fischer 344 rats 6-, 12- and 24-months of age. Cocaine (10(-6)M) and metanephrine (10(-5)M) were added to the perfusion fluid separately and in combination to block neuronal and extraneuronal uptake mechanisms, respectively. The amount of NE overflow in the effluent was significantly lower with increasing age at any given frequency of nerve stimulation. Metanephrine increased NE overflow in heart preparations of 12- and 24-month-old animals only. Yohimbine, a selective alpha 2 adrenoceptor antagonist at concentrations of 10(-6)M and 3 x 10(-6)M significantly increased the amount of NE overflow only in the perfusion effluent of hearts isolated from 6-month-old animals. These results suggest that extraneuronal uptake mechanisms increase with age and that presynaptic alpha 2 adrenoceptor-mediated autoregulation of NE decreases with age. The findings could account, at least in part, for the decrease in adrenergic control of the heart shown to occur with age.

In an effort to characterize rats as animal models for aging research, literature dealing with cardiovascular physiology and structure has been reviewed, and available data has been summarized in tabular form. The approach has been to present functional parameters on the basis of rat strain, age, sex, and experiemental condition, in the cases where these are known, so as to develop a unified reference source of baseline data. Hemodynamic properties, such as heart rate, cardiac output, blood pressure and related vascular parameters, have been found to change during the lifetime of rats in such a way as to make the cardiovascular system less efficient in meeting organismal requirements with increasing age. At the cellular level, changes in structure, electrophysiology, and contractile properties have been reported which could account, at least in part, for observed deterioration in cardiovascular function during aging.

To examine the renal effects of ibopamine HCl we evaluated 15 patients with New York Heart Association Class II-III congestive heart failure and mild renal insufficiency (creatinine clearance [CLCr] = 45-85 ml min-1). Diuretics and vasodilators were withheld and a sodium (Na+)-restricted diet was initiated. All patients exhibited positive Na+ balance at the time of evaluation. Hourly urine volumes, urine chemistries, serum chemistries, PAH and inulin/iothalamate clearances were determined 2 h pre and 4 h post a single 200 mg oral dose of ibopamine. Effective renal plasma flow, creatinine clearance, filtration fraction, and the fractional excretion of sodium and potassium were not significantly altered postdose. A significant increase in urine output and decrease in urine osmolality were seen at all time points postdose. A significant reduction in serum potassium (2 and 3 h) and blood urea nitrogen (1, 3 and 4 h) concentrations occurred.Measurements of glomerular filtration rate by inulin or [1251]-iothalamate produced differing results in the patient groups studied. We conclude that a single dose of ibopamine does not produce significant improvements in renal function in patients with congestive heart failure, mild renal insufficiency and positive sodium balance.

BackgroundOverweight (OW) and obesity (OB) are endemic in the United States and affect adolescents and adults with congenital heart disease (ACHD). Defining the burden of excess weight on the cardiovascular system in ACHD is the goal of this study. Limitation of exercise capacity due to overweight or obesity might be reversible with weight loss and improve quality of life for ACHD adults.MethodsExercise tests performed using a Bruce protocol and measurement of maximum oxygen consumption were retrospectively reviewed on 418 CHD patients. OW and OB were defined as the 85–95 or > 95 percentile respectively for age and gender or by adult criteria. Severity of CHD was assigned based on criteria published in standard guidelines.Results63 patients had mild, 198 moderate, and 157 severe heart disease. Each ACHD group was 32 to 34% OW or OB. Measured exercise time (ET) of CHD patients with moderate or severe heart disease was less than that of controls in each weight categories. However, OB or OW people have shorter ET than their normal weight peers with CHD. Multiple regression using ET as the dependent variable finds that female sex, relative BMI, and VE/VCO2 at peak exercise are all associated with lesser ET with high significance. Peak heart rate is associated with greater ET, with borderline significance. Severity of heart disease is not independently associated with ET.ConclusionsOW and OB are strongly associated with reduced ET in persons with congenital heart disease. Losing weight may improve exercise capacity in ACHD.

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Studies dealing with biochemistry of the central nervous system of rats have been reviewed. Data on the effects of age on enzyme activity and cellular substrates have been summarized in tabular form. In general, it can be concluded that biochemical functions dealing with anabolism decrease whereas those dealing with catabolism increase as aging progresses.

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