Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow.

The current study was performed to determine whether baroreflex resetting after acute administration of converting enzyme inhibitors (CEIs) was dependent on the concomitant decrease in mean arterial pressure (MAP). Reflex changes in lumbar sympathetic nerve activity (LSNA) due to increases and decreases in MAP [i.v. phenylephrine (PE) and nitroprusside infusions] were determined in normotensive and renal hypertensive (1-kidney, 1-clip) anesthetized WKY rats 1) before (control), 2) 15 min after intravenous captopril (2 mg/kg) or enalaprilat (300 micrograms), and 3) 15 min after MAP was returned to pre-CEI levels with intravenous PE. CEIs decreased MAP and caused a leftward shift of the MAP-LSNA curve toward a lower operating pressure range in all hypertensive and in one group of normotensive rats. The baroreflex curve remained shifted to the left even after MAP was restored to pre-CEI levels by infusion of PE. Thus CEIs cause a pressure-independent resetting of baroreflex control of sympathetic outflow within 15 min. This effect of CEIs is most likely due to elimination of a central nervous system effect of circulating angiotensin II and could contribute to the antihypertensive actions of this class of compounds.

Population characteristics and cigarette yield as determinants of smoke exposure.

Relationships of population characteristics, smoking history, and cigarette yield with smoke exposure as measured by peripheral blood concentrations of thiocyanate, carboxyhemoglobin, nicotine and cotinine were sought in 170 male smokers. This population of smokers had significant elevations of serum thiocyanate, blood carboxyhemoglobin and plasma nicotine and cotinine concentrations as compared with an equal number of age- and sex-matched nonsmokers and these concentrations correlated significantly with past 24-hour cigarette consumption. Although the nicotine yield of the cigarette correlated significantly with plasma cotinine and marginally with plasma nicotine, the reduction in plasma nicotine and cotinine was not proportionate to the reduced yield of the cigarettes, suggesting that smokers partially compensate for the lower yields of their cigarettes. Blood levels of carboxyhemoglobin, nicotine and cotinine were also significantly associated with the weight of the subjects, presumably due to the relationship between weight and the volume of distribution. Univariate and multiple regression analyses provided evidence that coffee and alcohol consumption and years smoked also may be important determinants of smoke exposure.

Puffing topography as a determinant of smoke exposure.

Puffing topography variables were measured in a well-characterized, male population smoking their own brand of cigarette. Of the puffing topography variables, interpuff interval appeared to be the primary determinant of blood concentrations of smoke constituents: however, preliminary data in a homogeneous population according to the nicotine yield of their cigarette suggest that total puff volume per cigarette may also be a significant determinant of blood levels of smoke constituents. Smokers of low nicotine yield cigarettes partially compensated for these lower yields by increasing the total volume puffed per cigarette. Observed differences in puffing topography associated with increased daily cigarette consumption and cumulative smoking history were consistent with a higher smoke exposure per cigarette. Further, although both alcohol and coffee consumption are associated with present and cumulative smoking history, coffee consumption is uniquely associated with differences in puffing topography consistent with a higher smoke exposure per cigarette. However, by multiple regression analyses, neither coffee nor alcohol consumption histories added significantly to the prediction of blood concentrations of smoke constituents over that obtained by smoking history and puffing topography.

An isolated upper airway preparation in conscious dogs.

The purpose of this study was to develop an isolated upper airway preparation in conscious dogs. Each of the four dogs was trained to wear an individually fitted respiratory mask and surgically prepared with two side-hole tracheostomies. After full recovery, one endotracheal tube was inserted caudally into the lower tracheostomy hole and another tube cranially into the upper tracheostomy. When the two endotracheal tubes were connected to a breathing circuit including a box-balloon system, the magnitude and pattern of the inspiratory flow through the upper airway were identical to that inhaled spontaneously into the lungs by the dogs, but the gas medium inhaled into the upper airway could be independently controlled. Thus it allowed test gas mixtures to be inhaled spontaneously through an isolated upper airway. One limitation was that the inspired gas remained in the upper airway during expiration, but this can be corrected by a simple modification of the breathing circuit. This preparation was tested in studying the respiratory effects of upper airway exposure to CO2 gas mixtures. Our results showed small but significant reduction in both rate and volume of respiration when the concentration of CO2 gas mixture inhaled through the upper airway exceeded 5%. Irregular breathing patterns were frequently elicited in these dogs by higher concentrations (greater than 12%) of CO2.

Smoking history, cigarette yield and smoking behavior as determinants of smoke exposure.

This study examines how smoking history, cigarette yield and smoking behavior relate to smoke exposure as determined by smoke constituents and their metabolic products in peripheral blood. Recruited without regard to the nicotine yield of their cigarette, male smokers smoked their own cigarettes ad libitum, including one cigarette five minutes prior to venipuncture. Smokers had significant (p = 0.0001) elevations of serum thiocyanate, blood carboxyhemoglobin, plasma nicotine, and cotinine concentrations each of which was significantly associated with past 24-hour cigarette consumption. The nicotine yield of the cigarette significantly correlated with plasma cotinine concentrations and with the smoking behavior variables. Most notably, smokers consuming lower nicotine yielding cigarettes exhibited an increased total puff volume per cigarette, suggesting that smokers of low nicotine yielding cigarettes compensate for these low yields by their smoking behavior. However, the fact that lower plasma cotinine concentrations are present in smokers of low-nicotine cigarettes suggests that this compensation is incomplete. That smoking behavior variables relate to smoke exposure was demonstrated by a significant linear correlation between plasma nicotine and mean puff interval in the total smoking population and between plasma nicotine and total puff volume per cigarette in a subpopulation smoking a single brand of cigarette. These data suggest that smoking history, nicotine yield of the cigarette and smoking behavior are all determinants of smoke exposure. Further, although smokers of low-yield cigarettes appear to compensate by puffing larger volumes per cigarette, this compensation appears to be inadequate to attain an equivalent smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Lower levels of vitamin C and carotenes in plasma of cigarette smokers.

Plasma levels of vitamins A, C, and E, selenium, and carotenes were determined in 125 male cigarette smokers and 125 age- and race-matched nonsmokers. The smokers had a mean daily consumption of 30.6 cigarettes and a cumulative consumption of 22.8 pack years. Plasma levels of vitamin C and total carotenes were significantly (p less than 0.05) lower in smokers than those of nonsmokers, while levels of vitamin A, selenium, and vitamin E were not significantly different between these two groups. Similar results were found when only those subjects not taking any form of dietary supplements were included for analysis. Except for negative correlation between vitamin A and pack-year, no significant correlates were observed between plasma levels of these micronutrients and indices of smoking status or cigarette consumption in smokers. These data suggest that chronic cigarette smoking is associated with depressed levels of plasma vitamin C and carotenes; however, the relationship between smoking and these plasma micronutrients is still unclear.

Nicotine exposure and Parkinson disease.

The observed inverse relationship between smoking and Parkinson disease has prompted suggestions that nicotine, a centrally active agent, might protect against the disease. In this case-control study, cases were found to have ever regularly smoked cigarettes significantly less frequently than sex-, race-, and age-matched neighbors. This report analyzes the detailed smoking histories of cases and neighbors to see if these histories support the nicotine protection hypothesis. Estimated nicotine exposure before age at onset of symptoms for smoking cases was 186.1 g; for smoking controls it was 208.3 g (p = 0.34). Among the cases, severity of disease was not related to the extent of nicotine exposure before disease onset. Age at onset of symptoms for smoking cases (52.7 years) was not delayed (57.8 years for nonsmoking cases). Since the study was unable th find further support for the nicotine protection hypothesis, it is concluded that the observed inverse relationship between smoking and Parkinson disease is likely explainable by other factors, such as selective mortality or pre-morbid behavioral and/or constitutional changes.