Effect of chronic cocaine administration and cocaine withdrawal on coronary flow rate and heart rate responses to epinephrine and cocaine in isolated perfused rat hearts.

The acute dose-dependent effects of epinephrine and cocaine on heart rate and coronary flow rate (CFR) were examined in isolated, perfused (Langendorff) rat hearts from animals: i) pretreated with daily cocaine injections (20 mg/kg/day) for 8 weeks; ii) after 2-day withdrawal from 8-week cocaine pretreatment; iii) vehicle-treated controls. Chronic cocaine (CC) hearts were significantly less sensitive to the chronotropic effects of epinephrine than control (C) or withdrawal (CW) hearts. CW hearts exhibited significantly higher heart rates in response to epinephrine than C and CC hearts. Epinephrine alone (2.5 x 10(-7) M) decreased CFR 11% (C), 9%(CC), 14%(CW) from respective baseline levels. Cocaine alone had no significant effect on CFR in C hearts but produced slight dose-dependent decrements in CFR in CC and particularly CW hearts at higher doses. Cocaine plus epinephrine markedly decreased CFR in all groups, particularly in CW hearts. The results indicate that chronic daily cocaine administration produces a functional tolerance of the heart to the chronotropic actions of epinephrine but a 2-day withdrawal from chronic cocaine results in a rebound supersensitivity to adrenergic stimulation and cocaine's sympathomimetic effects. In addition, cocaine produces only minor decrements in coronary flow in the rat heart, while cocaine acts synergisticallly with epinephrine to produce a marked decrease in CFR.

Increases in serum lipid and lipoprotein levels with movement from the supine to standing position in adult men and women.

The effect of movement from the supine to the standing position on the magnitude of change in serum lipid and lipoprotein levels and its impact on the prediction of risk for coronary heart disease was investigated in 23 male and 18 female subjects. The mean age and body weight of the men was 34 years and 93 kg, respectively, while those of women were 36 years and 71 kg. Thirty minutes of standing following thirty minutes in the supine position was associated with hemoconcentration and a significant (P less than 0.05) plasma volume reduction of -13.8% for men and women combined. Posture-related increases in serum lipids and lipoproteins were similar among both men and women and averaged +12% for triglycerides, +9.3% for total cholesterol, +9.0% for low-density lipoprotein + very low-density lipoprotein cholesterol, and +10.4% for high-density lipoprotein cholesterol. Among men, the latter increased from 41.4 to 45.6 mg X dl-1 while among women, the increase was from 58.0 to 64.3 mg X dl-1. The total cholesterol/high-density lipoprotein cholesterol ratio was unaffected by the change in body position, thus strengthening the reliability of this ratio as a coronary heart disease risk measure. Our findings indicate that body position at time of blood withdrawal significantly influences lipid and lipoprotein levels, and, depending on the absolute concentration values of total or high-density lipoprotein cholesterol, can alter the predictive risk for coronary heart disease. Heart disease. Heart disease risk based on the Framingham probability tables and the multiplier for high-density lipoprotein cholesterol is unaffected by the change in body position.

Influence of age and cold stress on plasma catecholamine levels in rats.

We measured arteria plasma concentrations of norepinephrine (NE) and epinephrine (E) in pentobarbital-anesthetized 3- and 24-month-old male F344 rats in basal (control) conditions and following acute cold exposure (6 h at 4 degrees C). Basal levels of circulating NE and E were also determined in 3- and 24-month-old Sprague-Dawley animals. Basal NE did not change between 3 and 24 months of age in either strain of rat, whereas older animals of both strains had significantly higher basal plasma E concentrations compared to younger counterparts. Cold exposure increased plasma NE approximately 100 pg . ml-1 above respective basal levels in 3- and 24-month-old F344 rats, suggesting no age-related differences in sympathetic nervous system reactivity to cold stress. Plasma E in young cold-stressed F344 animals was elevated approximately 336 pg . ml-1 (287%) over basal levels, and approximately 370 pg . ml-1 (155%) over basal levels in older animals, resulting in cold-induced circulating E concentrations of 515 +/- 90 pg . ml-1, and 1040 +/- 122 pg . ml-1 in 3- and 24-month-old animals, respectively. Thus, arterial plasma E concentration in older rats is significantly elevated, both in basal conditions and in response to acute cold stress, suggesting enhanced adrenal medullary activity with advancing age.

Influence of aging and tyrosine hydroxylase inhibition on tissue levels of norepinephrine during stress.

The effect of aging was evaluated on norepinephrine content of the heart (ventricles) and spleen of 3- and 24-month-old F344 and Sprague-Dawley rats utilizing a sensitive radioenzymatic assay. To assess sympathetic nervous system activity, the decline in organ norepinephrine content was compared in young and old F344 rats 6 hours after blockade of norepinephrine synthesis with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor. Three conditions were studied: (a) normal, (b) brief starvation (54 hours), and (c) cold exposure (6 hours, 4 degrees C). There was no significant age-related difference in steady state organ norepinephrine concentration. Based on the response to alpha-methyl-p-tyrosine, aging did not affect the rate of heart and spleen norepinephrine synthesis and, therefore, sympathetic nervous system impulse activity during normal or cold stress conditions. Starvation, however, did not suppress sympathetic nervous system activity to the heart in old animals, as it did in the young rats.

Starvation suppresses sympathoadrenal medullary response to cold exposure in rats.

The effect of 2 days (55 h) of starvation on the functional state of the sympathetic nervous system (SNS) and adrenal medulla in male rats was evaluated in both normal (24 degrees C) and cold (4 degrees C) environments. Fasting (24 degrees C) significantly decreased NE turnover in heart and spleen, and the concentration of plasma epinephrine (E) and norepinephrine (NE). Cold exposure in the fed animals significantly increased NE turnover in the heart and plasma E, but had no effect on plasma NE or spleen NE turnover compared to normal (no stress) conditions. Cardiac NE turnover was 50% less in fasted cold-stressed animals than in fed cold-stressed animals. Plasma E remained at low levels. Plasma concentration of free fatty acids was significantly elevated in the fasted state in both warm and cold environments. These results suggest that 2 days of starvation in adult male rats suppresses the activity of the SNS and adrenal medulla and interferes with the normal adrenergic response to cold stress. Moreover, E appears not to be essential for mobilization of fat stores for energy metabolism in the fasted state in either warm or moderately cold environments.

Effect of marihuana on cardiorespiratory responses to submaximal exercise.

Six male chronic marihuana (MH) users exercised on a bicycle ergometer for 15 min at approximately 50% VO2max under 3 conditions: (1) not smoking (control), (2) after smoking MH containing 7.5 mg (-) delta-9-tetrahydrocannabinol, and (3) after smoking placebo marihuana (PL). The MH was administered double-blind in a counterbalanced repeated-measures design. Heart rates (HRs), arterial blood pressures (BPs), pulmonary ventilation (VE), and oxygen uptake (VO2) were measured during exercise and 15 min recovery. PL had no effect on any of the physiologic variables. Smoking MH had no effect on systolic blood pressure (SBP), diastolic blood pressure (DBP), VE, or VO2, but did induce a marked increase in heart rate which persisted throughout exercise and recovery periods, averaging 34% higher than control values at rest, 18% higher during exercise, and up to 50% higher during recovery. MH smoking increased the product of HR x SBP in all circumstances.