Phenylpropanolamine constricts mouse and human blood vessels by preferentially activating alpha2-adrenoceptors

Phenylpropanolamine (dl-norephedrine) was one of the most widely used therapeutic agents to act on the sympathetic nervous system. Because of concerns regarding incidents of stroke, its use as a nasal decongestant was discontinued. Although considered an alpha1-adrenergic agonist, the vascular adrenergic pharmacology of phenylpropanolamine was not fully characterized. Unlike most other circulations, the vasculature of the nasal mucosa is highly enriched with constrictor alpha2-adrenoceptors. Therefore, experiments were performed to determine whether phenylpropanolamine activates vascular alpha2-adrenoceptors. Mouse tail and mesenteric small arteries and human small dermal veins were isolated and analyzed in a perfusion myograph. The selective alpha1-adrenergic agonist phenylephrine caused constriction of tail and mesenteric arteries and human veins. The selective alpha2-adrenergic agonist UK14,304 [5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine] caused constriction in tail arteries and in human veins, but not mesenteric arteries. The lack of constriction to UK14,304 was also observed in endothelium-denuded mesenteric arteries. Phenylpropanolamine constricted both types of artery but was 62-fold more potent in tail arteries. In mesenteric arteries, constriction to phenylpropanolamine was not affected by the selective alpha2-adrenergic antagonist, rauwolscine (10(-7) M) but was abolished by the selective alpha1-adrenergic antagonist, prazosin (3 x 10(-7) M). In contrast, constriction to phenylpropanolamine in tail arteries and in human veins was inhibited by rauwolscine but not prazosin. Therefore, phenylpropanolamine is a preferential alpha2-adrenergic agonist. At low concentrations, it constricts blood vessels that express functional alpha2-adrenoceptors, whereas at much higher concentrations, phenylpropanolamine also activates vascular alpha1-adrenoceptors. This action likely contributed to phenylpropanolamine's therapeutic activity, namely constriction of the nasal vasculature.     

Phenylpropanolamine increases plasma caffeine levels

The effects of the widely consumed drugs caffeine and phenylpropanolamine are mediated through activation of the central and sympathetic nervous systems. Severe, life-threatening, and occasionally fatal hypertensive reactions have been reported after their combined use. This study examined the possible pharmacokinetic interaction of phenylpropanolamine and caffeine. Sixteen normal subjects received combinations of caffeine, phenylpropanolamine, and placebo. In subjects receiving 400 mg caffeine plus 75 mg phenylpropanolamine, the mean (+/- SEM) peak plasma caffeine concentration of 8.0 +/- 2.2 micrograms/ml was significantly greater than after 400 mg caffeine alone (2.1 +/- 0.3 micrograms/ml; t[24] = 2.4; p less than 0.01). Physical side effects were more frequent after the phenylpropanolamine-caffeine combination than after either drug alone or after placebo. Greater increases in both systolic and diastolic blood pressures occurred after the combination than after either drug alone. Because caffeine levels can be increased greatly when certain other drugs are coconsumed, these data indicate that phenylpropanolamine may enhance absorption or inhibit elimination of caffeine and may explain increased side effects reported after their combined use.     

诊室偶测血压与自动电子血压计自测血压指导高血压治疗的对比研究

目的 :观察诊室偶测血压 (CBP)与自动电子血压计自测血压对高血压治疗的影响。方法 :45例治疗中的原发性高血压患者 ,用欧姆龙HEM 72 7型便携式电子血压计自测血压 ,每天 3次 ,分别于 7:3 0、11:3 0、16:0 0时 ,共 3 0d ,然后与CBP进行对比分析。结果 :CBP大于自测血压 ,两者差异有非常显著性 (P <0 0 1)。CBP以血压控制≤ 14 0 /90mmHg为满意 ,自测血压以血压控制≤ 13 5 /80mmHg为满意 ,CBP有 2 5例满意 ,自测血压有 3 5例满意 ,两者差异有显著性 (P <0 0 5 )。结论 :在指导高血压治疗中 ,自测血压较CBP更能反映患者的真实血压水平 ,前者是后者的重要补充 ,能更好地指导治疗 ,并提高患者对治疗的顺从性。建议高血压患者多使用高准确性的自动电子血压计自测血压     

Minerals and blood pressure

The mineral elements sodium, potassium, calcium and magnesium play a central role in the normal regulation of blood pressure. In particular, these mineral elements have important interrelationships in the control of arterial resistance. These elements, especially sodium and potassium, also regulate the fluid balance of the body and, hence, influence the cardiac output. Evidence shows that the present levels of intake of mineral elements are not optimum for maintaining normal blood pressure but predispose to the development of arterial hypertension. Research results suggest that without sodium chloride (common salt) and other sodium compounds being added to the diet arterial hypertension would be virtually non existent. Moreover, blood pressure would not rise with age. In communities with a high consumption of added sodium, a high intake of potassium and, possibly, magnesium seem to protect against the development of arterial hypertension and the rise of blood pressure with age. A marked reduction of sodium intake is effective in treating even severe hypertension. A moderate restriction of sodium intake or an increase in potassium intake exert remarkable antihypertensive effects, at least in some hypertensive patients. Magnesium and possibly also calcium supplements may be effective in reducing blood pressure in some hypertensives. In hypertensive patients treated with drugs sodium restriction and potassium and magnesium supplementation enhance the therapeutic effect, reduce the number and dosage, and lessen the adverse effects of prescribed antihypertensive drugs. Hence, a fall in sodium consumption and increases in potassium and magnesium consumption are useful in preventing and treating arterial hypertension.     

直接血压与间接血压相关性的影响因素与假性高血压的关系

目的探讨直接血压与间接血压的相关性及其影响因素与假性高血压的关系.方法 208例临床需要行冠状动脉造影的患者,男150例,女58例,平均年龄(60.2±10.9)岁.在动脉穿刺成功后冠状动脉造影前同步测量直接血压和间接血压各3次,取平均值,造影结果由2位以上专家判断并记录.根据冠状动脉造影结果分为2组,冠状动脉正常组(104例)和冠心病组(104例).根据有无高血压病分为正常血压组(95例)和高血压病组(113例).并测量身高、体质量、臂围(AC)、腰围(WC)、臀围(HC),计算体质量指数(BMI)、腰围/臀围(WHR)、腰围/身高(WHtR)、平均血压(MBP)、直接与间接收缩压(SBP)差值(S-S)和直接与间接舒张压(DBP)差值(D-D).结果①直接血压与间接血压明显相关,SBP、MBP、DBP相关系数分别为0.88、0.76、0.58(P＜0.01).②高血压病组、冠心病组、女性直接SBP与间接SBP相关性好,而直接DBP与间接DBP相关性较差, SBP、MBP、DBP相关系数分别为0.52、0.48、0.49(P＜0.01).③直接血压总体上高于间接血压,S-S:-39～40 mm Hg(1 mm Hg=0.133 kPa),(6.35±12.50) mm Hg;D-D:-47～55 mm Hg,(5.63±11.17) mm Hg. S-S≤-10 mm Hg组与S-S＞-10 mm Hg组,S-S≤-10 mm Hg组的 AC、WC、HC、WHR、WHtR、BMI和年龄是更高的,仅BMI差别有统计学意义(P＜0.05).D-D ≤-10 mm Hg组与D-D＞-10 mm Hg比较,D-D ≤-10 mm Hg组 AC,WC,HC,WHR,WHtR 和BMI是更高的,仅AC差别有统计学意义(P＜0.05).分析AC与直接间接SBP、DBP的差值的关系发现:冠心病组AC与D-D相关,相关系数为0.27(P＜0.01).高血压组S-S与AC相关,相关系数为-0.22(P＜0.05).结论①直接血压与间接血压有明显相关性,其中SBP相关性最好,MBP次之,DBP最差(尤其是高血压病组、冠心病组和女性组);②AC是影响直接与间接血压测量值差值的重要因素,冠心病组AC影响DBP,而高血压病组AC影响SBP;③BMI高和AC大者易高估间接血压而出现假性高血压的情况.     

Improved blood pressure control with a physician-nurse team and home blood pressure measurement

OBJECTIVE: To assess whether a physician-nurse team model could improve long-term hypertension control rates by active intervention and modification of antihypertensive drug regimens based on home blood pressure (BP) measurements. PATIENTS AND METHODS: This study consisted of patients referred to a hypertension specialty clinic between July 1999 and June 2002 for the evaluation and management of uncontrolled hypertension. Patients were evaluated initially by a physician. A treatment plan was designed and implemented subsequently by a hypertension nurse specialist. Each patient was given an automated digital home BP monitor and requested to provide 42 BP readings taken during 7 days at intervals of 1, 3, 6, 9, and 12 months after dismissal from the clinic. The mean of these weekly values was reviewed by the physician-nurse team, and the treatment regimen was adjusted to achieve a goal BP of less than 135/85 mm Hg. RESULTS: One hundred six consecutively referred patients were enrolled in the study (mean+/-SD age, 64+/-14 years; 58% female; baseline BP, 156+/-16/85+/-11 mm Hg). Ninety-four patients submitted BP data after 1 month, and 78 patients completed the entire 12-month study period. Overall, mean BP decreased to 138+/-17/78+/-8 mm Hg at 1 month and to 131+/-9/75+/-7 mm Hg at 12 months (P<.01 vs baseline). The percentage of patients who achieved BP control to less than 135/85 mm Hg increased from 0% at baseline to 63% at 12 months. Intensification of antihypertensive drug therapy was required, on average, in 24% of patients at each study interval. The mean number of drugs increased from 1.2 at baseline to 2.0 at 12 months (P<.01). CONCLUSION: The use of home BP measurement by a physician-nurse team has the potential to significantly improve long-term hypertension control rates in a geographically dispersed patient population. This model should reduce both cost and inconvenience associated with the treatment of hypertension.     

Stroke and blood pressure variability

Sleep apnoea is associated with increased cardiovascular risk. Sleep apnoea is common after stroke and associated with increased blood pressure variability as described by Turkington and co-workers in this issue of Clinical Science. Both sleep apnoea and blood pressure variability confer a poor prognosis after stroke and are potentially treatable. Many studies of CPAP (continuous positive airway pressure) demonstrate decreases in cardiovascular risk markers in other patient groups. Although difficult to apply in these patients in the short term, CPAP has some potential benefits in medium-term rehabilitation and secondary prevention following stroke, which warrants further study.