ANTIHYPERTENSIVE EFFECTS OF MESULERGINE: FURTHER EVIDENCE FOR A PERIPHERAL SITE OF ACTION OF DOPAMINE AGONISTS

The cardiovascular effects of mesulergine were studied in anesthetized dogs. Intravenous (IV) administration (0.3 mg/kg) significantly decreased blood pressure in neurogenic hypertensive dogs without any change in heart rate. This effect was completely antagonized by IV administration of domperidone (0.5 mg/kg). Intracisternal administration of mesulergine (0.03, 0.3 and 3 mg/kg) did not produce any change in blood pressure. However, with the highest dose we observed a significant rise in heart rate during the first 2 min (which was probably nonspecific). These results suggest that mesulergine lowers blood pressure in sinoaortic-denervated dogs by means of a peripheral mechanism probably involving DA2 receptors. The findings confirm the potential interest of dopamine-receptor agonists as future antihypertensive agents.     

Calculation of Hydrolytic Rate Constants of Poly(ortho ester)s from Molecular Weights Determined by Gel Permeation Chromatography

Purpose. To obtained rate constants from weight-averaged (M_w) or z-averaged (M_z) molecular weights for polymers of Schule-Flory distribution and undergoing random scission. These constants were compared with those obtained by parallel ¹HNMR studies. Methods. The hydrolysis of two poly(ortho ester)s were followed by ¹HNMR and gel permeation chromatography (GPC). Results. Equations to convert number-averaged (M_n), M_w and M_z into fraction of backbone remaining (f_c) were derived. First-order hydrolytic rate constants of two poly(ortho ester)s; DETOSU-HD and DETOSU-CDM were calculated using these relationships. The rate constants calculated from ¹HNMR, M_z and M_w were 0.215, 0.218 and 0.182 hr^–1, respectively, for DETOSU-CDM and 0.152, 0.086 and 0.038 hr^–l for DETOSU-HD. The large discrepancy in the rates determined by ¹HNMR and GPC in the latter case was attributed to that the detector response (refractive index) of the monomers was lower than that of the high molecular weight polymer. The difference is small in the case of DETOSU-CDM, and the rates calculated from GPC data were comparable or nearly identical to that obtained from ¹HNMR data. Conclusions. Although GPC can yield rapid and valuable kinetic data for the degradation of biodegradable polymers, the system, however, must be carefully calibrated to account for the variations in Mark-Houwink coefficients and in the response of the mass detector between the high and low MW polymers.     

Ten-year stability of cardiovascular responses to laboratory stressors

In this study we examined test-retest stability of cardiovascular stress responses over a decade of the life span. Participants were 55 male college undergraduates. 19 years of age at initial testing, and 29 years of age at follow-up testing Stressors were a foot cold pressor and an aversive reaction time task. Cardiovascular measures included systolic and diastolic blood pressure, heart rate, and preejection period. For cold pressor, the magnitude and pattern of cardiovascular responses remained unchanged at the 10-year follow-up. For the reaction time task, the characteristic cardiovascular response patterns was preserved but with significant attenuation of magnitude. The present findings are consistent with previous observations of temporal stability but over a substantially longer test-retest interval. The long-term stability of stress responses is discussed in the context of stress test methodology, behavioral response demands, and maturation of the physiological systems involved in cardiovascular response expression.     

Heart rate fluctuations in diabetic patients with cardiac vagal dysfunction: a spectral analysis

The autonomic nervous control of cardiac function during active orthostatic load has been studied by measuring the power spectrum of heart rate fluctuations in 16 insulin-dependent diabetic patients and 14 age-matched control subjects. The patients were subdivided into two groups: 8 with normal respiratory sinus dysrhythmia (RSA+) and 8 with reduced respiratory sinus dysrhythmia (RSA-). In RSA- patients the total power (0.01-0.50 Hz) was significantly reduced compared with control subjects (4.7 versus 15.5 min-2, 2p less than 0.05) and the pattern of heart rate fluctuations was characterized by a relative increase in the low-frequency component (0.01-0.05 Hz) as compared with RSA+ patients and control subjects (45% versus 24% and 27%, both 2p less than 0.01). There was also a significant reduction in the high-frequency component (0.15-0.50 Hz) as compared with RSA+ patients and control subjects (17% versus 36% and 33%, both 2p less than 0.05). During standing, a significant increase in total power was found only in control subjects (2p less than 0.01) and the difference between control subjects, and RSA+ and RSA- patients reached significance (32.2 versus 15.1 and 12.7 min-2, 2p less than 0.02 and 2p less than 0.01). The pattern of heart rate fluctuations in RSA- patients showed no significant change on standing. These results suggest that the reduced overall heart rate variability in diabetic patients with cardiac autonomic neuropathy is associated with a typical heart rate fluctuation pattern.     

CROMAKALIM SUPPRESSES HYPERTONIC SALINE-INDUCED RENAL VASOCONSTRICTION IN ANAESTHETIZED DOGS

1. Intrarenal arterial infusion of hypertonic saline (HS) transiently increased and then gradually reduced renal blood flow (RBF) in anaesthetized dogs. Glomerular filtration rate (GFR) but not filtration fraction decreased at the end of the infusion. 2. In the presence of a potassium channel opener cromakalim (0.3 μg/kg per min), HS infusion failed to reduce RBF; the initial increase in RBF was maintained throughout the infusion. Since cromakalim also prevented the decrease in GFR, HS infusion lowered filtration fraction. 3. The results suggest that cromakalim inhibits both pre-and postglomerular vasoconstriction induced by HS infusion.     

Aptitude for physical exercise in a population of female hospital workers

Summary The aim of this study was to evaluate the level of physical capacity in a female hospital population of Paris and its suburbs. A total of 1505 women working in the selected departments filled in a questionnaire concerning their working conditions, life habits and health and also attended a medical examination. The effort test performed consisted in flexing the legs 20 times with the chest held straigt, in 40 s. The heart rates were measured for the first, the second and the third minutes of recovery (first 15 s multiplied by 4). The blood pressure was measured just after the heart rate, for the first and the third minute. Recovery indices have been constituted from the results. The respective weights of anthropometric and sociodemographic risk factors for recovery indices were studied in multiple logistic regression models. The classification enables us to consider about 25%–30% of our population as having a satisfactory physical capacity, about 26%–27% as having an acceptable capacit, and about 24%–27% as having a weak capacity. About 21% of the population presented an excessive pressure reaction and 44% a questionable pressure reaction. Our results concerning the level of physical capacity of the female nursing staff should be taken into account especially in the future planning of work loads and architectural choices, which must avoid excessive physical burdens in relation to this level. An improvement in the level of physical capacity could be envisaged as well.     

Exhaled nitric oxide in healthy children: Variability and a lack of correlation with atopy

Nitric oxide (NO) is a free radical produced by several lung cells via the enzyme nitric oxide synthetase (NOS) and can be easily measured in exhaled air by chemiluminescence analysis. As the iso-enzyme iNOS may be induced by cytokines and endotoxin, NO is elevated in several chronic inflammatory airway diseases. Prior to using exhaled nitric oxide (eNO) as a non-invasive marker of airway inflammation in daily routine, the role of possibly influencing factors such as age, time of the day, smoking exposure and intra-individual variability have to be clarified. NO concentrations were measured in 107 healthy children aged 4–18 years at an expiratory flow of 184 ml/s. Spirometry and a skin-prick test were performed and a questionnaire on family history of atopy, personal symptoms of atopic disease and smoke exposure was completed. For intra-individual variability nitric oxide was measured in six children three times daily on 6 consecutive days. Median eNO concentration was 5.7 p.p.b., and increased significantly with age but did not vary with gender. No correlation was found between eNO and smoke exposure, positive skin-prick test, FEV ₁, MEF₂₅ and time of the day. There was no circadian rhythm found in the six children measured on 6 consecutive days, but the eNO showed an intra-individual coefficient of variation of 25.9%. With the help of a two-compartment model of the lung the alveolar NO concentration was estimated to be 4.1 p.p.b and was shown to be constant with age, whereas the airway part of NO steadily increased with age. When comparing eNO values with standardized measurement techniques, the age of the children and the large intra-subject coefficient of variation have to be taken into account, whereas in healthy children subject-specific factors such as atopic history, gender and skin test reactivity did not affect eNO measurement.     

Eyelid movements during blinking in patients with Parkinson's disease.

We examined eyelid movements during spontaneous, voluntary, and trigeminal reflex blinks in 16 patients with mild to moderate Parkinson's disease (PD) off medication and 14 controls. Voluntary and reflex blink amplitudes tended to be smaller than normal for PD patients, whereas eyelid kinematics (amplitude-maximum velocity relationship) for all three blink types were normal. Spontaneous blink rate was less than normal for 10 patients and abnormally high for 6 patients. A significant positive correlation between spontaneous blink amplitude and blink rate was found. These observations suggest that PD modifies the gain of a premotor blink circuit shared by spontaneous, voluntary, and reflex blinks.