RELATIONSHIP OF CIGARETTE SMOKING TO BLOOD PRESSURE AND SERUM LIPIDS AND LIPOPROTEINS IN MEN

1. The relationship of cigarette smoking to blood pressure and serum lipids and lipoproteins was studied in 7608 men, ranging from 40 to 59 years of age. Analyses were performed separately for non-drinkers and drinkers. 2. After adjusting age and body mass index (BMI) in non-drinkers and age, BMI and alcohol intake in drinkers in forward stepwise multiple regression analysis, there was a dose-dependent negative relationship between cigarette smoking and diastolic blood pressure (DBP) and high density lipoprotein cholesterol (HDL-C), regardless of drinking habit. There was a dose-dependent positive relationship between cigarette smoking and the ratio of total cholesterol (TC) to HDL-C (TC:HDL-C) in non-drinkers, but not in drinkers. There was a dose-dependent negative relationship between cigarette smoking and TC and a positive relationship between cigarette smoking and triglycerides (TG) in drinkers, but not in non-drinkers. 3. After matching age and BMI in non-drinkers, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of systolic blood pressure (SBP; 4.3%; P<0.05), DBP (3.0%;P<0.01) and HDL-C (15.5%;P<0.01) and higher mean values of TC:HDL-C (25.0%;P<0.01), TG (46.8%; P<0.01) and β-lipoprotein (12.0%; P<0.01) than non-smokers. In drinkers, after matching age, BMI, and alcohol intake, subjects who smoked more than 30 cigarettes/day had significantly lower mean values of SBP (2.8%; P<0.05), DBP (4.8%; P<0.01), HDL-C (17.3%; P<0.01) and TC (4.4%; P<0.01) and higher mean values of TC:HDL-C (15.4%; P<0.01) and TG (45.1%;P<0.01) than non-smokers. 4. Although the results are somewhat variable, the present study reveals that cigarette smoking is negatively associated with SBP and DBP and unfavourably associated with lipids and lipoproteins, regardless of drinking habit.     

DISSOCIATION OF BLOOD PRESSURE AND ALBUMINURIA IN NORMAL SUBJECTS INFUSED WITH ANGIOTENSIN II AND NORADRENALINE

1. Albuminuria is a predictor of diabetic renal disease and atherosclerosis. Changes in blood pressure (BP) may influence albuminuria. 2. The effect of acute BP elevation on albumin excretion rates (AER) using noradrenaline (NA) and angiotensin II (AII) infusions in six normal subjects was examined. 3. The average rise in BP during a 120 min infusion was 23 mmHg for AII and 16 mmHg for NA. 4. There was a marked dissociation between AER and BP levels in both AII and NA infusions. 5. Previously described correlations between BP and AER in ambulatory BP studies may be explained by other factors such as exercise and postural changes.     

EFFECT OF PURE EICOSAPENTAENOIC ACID FEEDING ON BLOOD PRESSURE AND VASCULAR REACTIVITY IN SPONTANEOUSLY HYPERTENSIVE RATS

1. This study examined the effects of eicosapentaenoic acid (EPA) treatment on vascular reactivity and blood pressure in spontaneously hypertensive rats (SHR). 2. Twenty SHR were given pure EPA as the methyl ester (280 mg/kg) by gavage for 10 days. An equal number of control rats received vehicle alone. EPA treatment had no effect on blood pressure compared with control rats. 3. Aortic rings from EPA-treated rats, precontracted with PGF2 alpha showed increased endothelium-dependent relaxations to acetylcholine. Endothelium-independent relaxations to sodium nitroprusside were not altered. Rings from rats fed pure EPA did not show any differences in vasoconstrictor responses to noradrenaline or serotonin. 4. Serum thromboxane B2 (TXB2) levels fell 17% in animals given pure EPA, but prostacyclin production was not affected. These responses are less than those seen following Max EPA fish oil. 5. Thus, pure EPA treatment did not lower blood pressure, but may have a direct effect on aortic endothelia and cause increased endothelium-dependent relaxations in response to acetylcholine in SHR.     

'SALT SENSITIVITY' OF NORMOTENSIVES: INTERACTIONS BETWEEN CHANGES IN RED BLOOD CELL 22Na EFFLUX RATE CONSTANT, DIETARY SODIUM INTAKE AND CHANGES IN BLOOD PRESSURE

1. In normotensive people who altered dietary sodium intake there was no overall difference in blood pressure or efflux rate constant when on a low or high sodium intake. 2. Many individuals studied had changes in blood pressure or efflux rate constant greater than the expected variation. 3. Subjects were classified into three groups depending on the change in efflux rate constant. Seven subjects who had a fall in the efflux rate constant greater than 0.02 h when they changed from a low to a high sodium intake had a significant rise in diastolic blood pressure (73, s.e.m. =4; to 80, s.e.m. =3 mmHg). 4. Eight subjects who had a rise in the efflux rate constant greater than 0.02 h when they changed from a low to a high sodium intake had a significant fall in diastolic pressure (82, s.e.m. =4; to 76, s.e.m. =4 mmHg). 5. Eight subjects who had no change in efflux rate constant when they changed from a low to a high sodium intake had no significant change in blood pressure. 6. The above associations were found when the red blood cells were incubated in plasma. No association was found when the cells were incubated in artificial medium. 7. The data supports the hypothesis that changes in membrane Na transport have a role in the control of blood pressure. 8. It is postulated that normotensive subjects who had a decreased efflux rate constant when exposed to a high sodium intake may develop essential hypertension.     

THE EFFECT OF DIETARY FISH OIL AND LONG-TERM SALT LOADING ON BLOOD PRESSURE AND EICOSANOID METABOLISM IN SPONTANEOUSLY HYPERTENSIVE RATS

1. Dietary suppression of prostanoid synthesis with fish oils has had little effect on blood pressure in models of experimental hypertension in rats. However, a pressor effect of dietary fish oils was observed in spontaneously hypertensive rats (SHR) subject to 1 week of salt loading. 2. Animals were allocated to semisynthetic diets containing either 10% by weight Max EPA fish oil or a control diet of coconut oil, and studied after receiving 1.5% saline for 4 weeks. 3. Within the first week of salt loading, SHR-fed fish oil showed an increase in blood pressure (mean = 9 mmHg) relative to controls. This effect was transient, and after the first week of salt loading there was little difference in blood pressure between the two dietary groups. 4. Following dietary treatment there were substantial changes in plasma fatty acid composition with a 48% decrease in arachidonic acid content of fish oil-fed rats compared with control animals. Rats on the fish oil diet showed a threefold decrease in serum thromboxane generation. Prostacyclin production by incubated segments of aorta was reduced by more than 50% compared with the coconut oil-fed control group. 5. SHR on the fish oil diet showed increased urine volume and sodium excretion, presumably due to increased fluid and salt intake. 6. This study shows that dietary suppression of prostacyclin synthesis is associated with only a minor effect on blood pressure in long-term salt loading of SHR.     

EFFECTS ON SHEEP BLOOD PRESSURE OF TREATMENT WITH ANGIOTENSIN, STEROIDS AND SALT

1. Angiotensin II (AII, 0.22 microgram/min) infused for 7-14 days, into adult unanaesthetized wethers, caused a rise in blood pressure of 7 +/- 3/7 +/- 3 mmHg (mean +/- s.e.m.) from control values of 90 +/- 5/54 +/- 3 mmHg (P less than 0.05, n = 11). Cardiac output and pulse interval were not affected. A high salt intake had no effect on blood pressure, cardiac output and pulse interval, nor did it potentiate the action of AII. 2. Ethinyl oestradiol (EE, 20 mg/week) caused a small fall in systolic and diastolic pressure of 6 +/- 3/6 +/- 5 mmHg (n = 7, P less than 0.1, P less than 0.05). When AII (0.22 microgram/min) was given with EE, it still caused a significant rise in blood pressure (P less than 0.01). The synthetic progestin (1 mg of norethisterone [NE] for 8-18 days) plus a high salt diet had no effect on arterial pressure and cardiac output but pulse interval rose significantly (P less than 0.05). 3. Therefore the reduction in vascular reactivity to angiotensin seen in human pregnancy is probably not related to high levels of oestrogen. Further, NE combined with a high salt diet does not cause hypertension in sheep.     

VOLUNTARY BLOOD PRESSURE CONTROL USING CONTINUOUS SYSTOLIC BLOOD PRESSURE BIOFEEDBACK

1. Ability to alter blood pressure (BP) acutely with continuous systolic (SBP) BP biofeedback was assessed in volunteers using a new non-invasive finger BP monitor. 2. Reliability of finger BP measurement was demonstrated in six hypertensive subjects (21-60 years), by beat-to-beat comparison with brachial intra-arterial BP over 90 min. Wide variation of BP was achieved by physiological manoeuvres. Mean error of finger BP was -3.0/-2.2 mmHg with intra-subject s.d. of 7.2/5.4 mmHg. 3. Thirteen normotensives (21-51 years) were paid to undergo 30 trials of SBP biofeedback in six sessions over 3 weeks. The SBP trend was displayed on a monitor with appropriately 'shaped' targets; each trial consisted of BP-raising and -lowering periods of 45 and 90 s respectively with intervening 45 s baselines. 4. Nine subjects raised BP, on analysis of the last 10 trials, by an average of 18.8 mmHg while five of the 13 successfully lowered BP by an average of 10.0 mmHg. BP lowering was best achieved by diminishing respiratory rate and depth, and muscular relaxation. 5. Demonstration of large BP reductions in five of 13 normotensives using strategies applicable to longer training sessions warrants further investigations in hypertensive subjects, focusing on mediating mechanisms and transfer of effect beyond the laboratory.     

INTERACTIONS BETWEEN METHAQUALONE AND ETHANOL IN RATS AND MICE DURING ACUTE AND CHRONIC STATES

1. The effects of acute and chronic treatment of methaqualone on ethanol preference, the rate of disappearance of ethanol and on toxicity were studied in mice and rats. 2. Acute treatment with methaqualone showed a dose-dependent suppression in the voluntary intake of ethanol in C57B1/6J mice and rats. No significant change in ethanol intake was observed during chronic methaqualone treatment and withdrawal. 3. Methaqualone pretreatment significantly (P < 0.005) delayed the disappearance of ethanol in the blood and brain over a period of 50 to 200 min after a loading dose of 2.0 g/kg, i.p., of ethanol. 4. Methaqualone pretreatment at doses of 140 and 200 mg/kg significantly increased ethanol toxicity by 11% and 28%, respectively. Co-administration of ethanol using 6.0, 7.0 and 8.0 g/kg also reduced the LD₅₀ of methaqualone by 19%, 24% and 40%, respectively. 5. Chronic administration with ethanol decreased the toxicity due to methaqualone. Potentiation of ethanol toxicity by methaqualone may be of clinical importance in view of the narrow range of safety margin of ethanol.     

CIRCADIAN VARIATIONS OF BLOOD PRESSURE AND PULSE RATE IN ESSENTIAL HYPERTENSIVES WITH DIABETES MELLITUS

1. The circadian variations of blood pressure and pulse rate in essential hypertensives either with or without diabetes mellitus were studied. 2. Diabetic patients with orthostatic hypotension showed an increase in variability of blood pressure and a decrease in that of pulse rate when assessed by coefficient of variation. Cosinor analysis showed no significant circadian rhythm in both blood pressure and pulse rate in these patients. 3. There were no differences in the circadian variations of blood pressure and pulse rate between essential hypertensives with and without diabetes mellitus unless orthostatic hypotension was present. 4. These results suggest that diabetes mellitus per se does not have any effects on the circadian variations of blood pressure and pulse rate in essential hypertensives unless autonomic neuropathy is present.     

EFFECTS OF CENTRAL SEROTONIN NERVE LESIONS ON BLOOD PRESSURE IN NORMOTENSIVE AND HYPERTENSIVE RATS

1 Separate ascending and descending pathways of serotonin (5-hy-droxytryptamine, 5-HT) nerves in the rat central nervous system have been selectively lesioned by Idealized intracerebral administration of 5,7-dihydroxytryptamine (5,7-DHT) after pretreatment with desipramine (DMI). 2 Bilateral injections of 5,7-DHT into the medial forebrain bundle or the cervical spinal cord caused extensive losses of 5-HT and tryptophan hydroxylase in the anterior hypothalamus and thoracic spinal cord, respectively, without affecting noradrenaline (NA) levels. 3 The hypothalamic lesions caused only a slight, transient reduction of systolic blood pressure in normotensive rats. 4 A more pronounced and sustained hypotension occurred in normotensive rats but not in hypertensive rats after the spinal lesions.     

PLASMA AND PITUITARY PROLACTIN AND BLOOD PRESSURE IN BROMOCRIPTINE-TREATED SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar-Kyoto rats (WKY). 2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine-treated group compared with the lack of a change in BP observed in the vehicle-treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine-treated group than in the vehicle-treated group. 3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL. 4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY. 5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.     

ENZYME INDUCTION BY EATING CHARCOAL-GRILLED STEAK WITH NO EFFECT ON BLOOD LIPIDS

1. There has been interest in the suggestion that enzyme-inducing drugs, such as anticonvulsants, may produce beneficial changes in lipoprotein levels, in particular a rise in the ratio of high density lipoprotein cholesterol to total cholesterol. 2. This controlled study observed the effects of diets of charcoal or oven-cooked beef on antipyrine clearance (a commonly used measure of drug metabolizing capacity), the apparent oral clearance of phenacetin (a measure of cytochrome P448-dependent enzyme activity) and blood lipids in 18 healthy volunteers. 3. Charcoal-cooked beef increased antipyrine clearance by an average of 20% (P less than 0.059) and increased the apparent oral clearance of phenacetin fivefold (P less than 0.01). In contrast, oven-cooked beef did not significantly alter either measure of microsomal function. Neither diet had any effects on blood lipids. 4. We conclude that the type and degree of enzyme induction achieved by this type of dietary manipulation does not produce beneficial changes in lipoprotein profiles. A previously noted rise in high density lipoprotein cholesterol levels in volunteers fed charcoal-cooked beef may have been due to the effects of charcoal formed by charring of the beef during cooking.     

MIGRATION-INDUCED CHANGES IN BLOOD PRESSURE: A CONTROLLED LONGITUDINAL STUDY

A longitudinal study of the effects of migration on blood pressure and related factors is being carried out in members of a black Kenyan population who migrate from a traditional rural community to an urban environment. Data on the first 139 migrants (78 male, 61 female) and 204 control non-migrants (126 male, 78 female) who have been followed up for a period of 6 months are presented. Blood pressure changes rapidly on migration (within the first 2 months); thereafter trends between migrants and controls differ. Significant differences in systolic pressure between migrants and controls are found at all examinations during the 6 month follow-up in both sexes. Diastolic pressure falls in controls but rises in migrants, the greatest difference being seen at the 6 month examination. Migration is associated with a marked increase in dietary sodium and a fall in potassium demonstrated by measurements of urinary electrolyte excretion in 3 X 12 h or 3 X 24 h urine collections. Analysis of covariance shows that the blood pressure differences between migrants and controls are partly explained by urinary sodium/potassium ratios and in some instances by body weight.     

褪黑激素对吗啡成瘾大鼠戒断后的血压和心率的影响

采用皮下递增注射吗啡5d后,经纳络酮催瘾建立吗啡戒断模型。观察褪黑激素(melatonin,MT)对吗啡成瘾大鼠戒断后平均动脉血压(mABP)和心率(HR)的影响。结果表明,MT有明显抑制吗啡成瘾大鼠戒断后的高血压症和心加速症的作用,并呈剂量 效应关系。im α-受体阻断剂regitine能完全阻断吗啡戒断后mABP的升高。此外,吗啡成瘾大鼠血清中去甲肾上腺素的含量较正常大鼠高,MT可使之降至正常水平。因此,我们认为吗啡戒断时出现的高血压症与心动过速症与交感神经系统活动亢进有关,MT对吗啡戒断时心血管反应的抑制可能是通过抑制交感系统而实现。     

褪黑激素对吗啡成瘾大鼠戒断后的血压和心率的影响

采用皮下递增注射吗啡５ｄ后，经纳络酮催瘾建立吗啡戒断模型。观察褪黑激素（ｍｅｌａｔｏｎｉｎ，ＭＴ）对吗啡成瘾大鼠戒断后平均动脉血压（ｍＡＢＰ）和心率（ＨＲ）的影响。结果表明，ＭＴ有明显抑制吗啡成瘾大鼠戒断后的高血压症和心加速症的作用，并呈剂量效应关系。ｉｍα受体阻断剂ｒｅｇｉｔｉｎｅ能完全阻断吗啡戒断后ｍＡＢＰ的升高。此外，吗啡成瘾大鼠血清中去甲肾上腺素的含量较正常大鼠高，ＭＴ可使之降至正常水平。因此，我们认为吗啡戒断时出现的高血压症与心动过速症与交感神经系统活动亢进有关，ＭＴ对吗啡戒断时心血管反应的抑制可能是通过抑制交感系统而实现。     

RITANSERIN AND SEROTONERGIC MECHANISMS IN BLOOD PRESSURE AND FLUID REGULATION IN SHEEP

1. In previous studies, exogenous serotonin (5-HT), administered intravenously, caused dose-related increases in mean arterial pressure and heart rate in conscious sheep. The 5-HT2 antagonist ketanserin (0.1 mg/kg per h, i.v.) was shown to lower blood pressure in the conscious sheep primarily through antagonism of alpha-adrenoceptors. 2. A newer 5-HT2 antagonist, ritanserin, is a more selective antagonist in vivo, as it attenuated or abolished pressor responses to exogenous 5-HT, but not to phenylephrine. 3. When infused alone, ritanserin (0.1 mg/kg per h, i.v.) failed to produce a decrease in blood pressure, suggesting that 5-HT antagonistic properties are not sufficient by themselves to lower blood pressure. 4. Ritanserin displayed a different metabolic profile to ketanserin, with a markedly decreased water intake. The mechanism of this effect is unresolved, but may imply a permissive role for 5-HT in the modulation of drinking responses in the sheep. 5. Ritanserin did not modify ACTH-induced hypertension in sheep.     

EFFECT OF ADRENOCORTICAL STEROIDS AND THEIR STRUCTURAL ANALOGUES ON BLOOD PRESSURE IN SHEEP

1. A model of adrenocortical steroid-induced hypertension based on the effects of ACTH administration has been developed in sheep. The present studies examine the effects of a number of different steroid hormones on blood pressure to investigate their structure-activity relationships. 2. Infusion of the major ovine adrenal steroid hormones (combined steroid infusion of Cortisol, corticosterone, 11-deoxycortisol, aldosterone, deoxycorticosterone) reproduced the metabolic but not the blood pressure effects of ACTH. 3. Addition of 17α, 20α-dihydroxyprogesterone and 17α-hydroxyprogester-one, at rates appropriate for conditions of ACTH stimulation, to the combined steroid infusion reproduced both the blood pressure and metabolic effects of ACTH. 4. 17α, 20β-Dihydroxyprogesterone, 20β-dihydroxy-11-deoxycortisol and 20β-hydroxycortisol all had additional hypertensive activity when given with combined steroid infusion, but 16α-hydroxyprogesterone, 11β, 17α-dihydroxy-progesterone, 20a-hydroxyprogesterone and 20α-hydroxyprogesterone did not. 5. These studies support the concept of a new class of steroid hormone action in blood pressure regulation.     

24 HOUR AMBULATORY BLOOD PRESSURE PROFILES IN THE ACUTE PHASE OF STROKE

1. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was used to evaluate the blood pressure (BP) changes in acute stroke. 2. Stroke was categorized according to the probable underlying vascular mechanism into lacunar infarction (L), thrombotic infarction (T) and intracerebral haemorrhage (ICH). A total of 37 stroke patients were studied (T = 21, L = 9, ICH = 7). Control patients (n= 15) were acute medical admissions not severely ill or in significant pain. ABPM was performed on day 1 and day 7 following admission. 3. Day 1 mean ± s.d. 24h systolic BP (SBP) were L (159 ± 15.8), ICH (151 ± 33.4), T (147 ± 15.2) and controls (134 ± 17.8). Day 7 mean 24h SBP were L (138 ± 9.8), ICH (143 ± 26.9), T (138 ± 19) and controls (134 ± 14.8). In each stroke group BP fell to levels similar to control on day 7, while control mean SBP remained unchanged between days 1 and 7. The highest day 1 BP and the greatest subsequent fall on day 7 occurred for lacunar infarction. Diastolic BP showed similar changes to SBP. 4. The acute stress of hospitalization does not appear to explain elevated BP in acute stroke. Lacunar infarction appears to be particularly associated with temporary BP elevation.