Localization of tritiated norepinephrine in vascular sympathetic axons of the rat intestine and mesentery by electron microscope radioautography.

The distribution of infused tritiated norepinephrine (NE-(3)H) in small mesenteric arteries and intestinal arterioles in rats was investigated with electron microscopic radioautography. Silver grains, indicating the presence of the tritium label on the sections, were found lying mainly over axon bundles, but some were present over collagen and smooth muscle cells. Axons with the highest concentrations of silver grains had been sectioned at points where they were naked of Schwann cell sheath, were dilated into varicosities, and contained small granular vesicles. This finding was taken as confirmatory circumstantial evidence that the small granular vesicles were the sites of uptake and storage of NE. The short interval between the start of infusion and the fixation of the tissue appeared to rule out any process other than a direct uptake of NE by the peripheral axons. If axonal sites of uptake of NE-(3)H correspond to sites of release of NE, then the evidence suggests that such sites of release are widespread over the terminal part of the axon and are not confined to those parts of the axon which are in close contact with smooth muscle cells. Since the fixation and embedding procedures will remove NE which is not strongly bound to tissues, the localization of NE-(3)H in the radioautographs does not necessarily correspond to the distribution of all the NE present in vivo.

Transverse tubule apertures in mammalian myocardial cells: surface array.

The technique of " freezeetching" tissues for electron microscopy has permitted observation of the external apertures of the transverse tubules. The apertures appear on the cell surface in approximately parallel rows, which can be interpreted as corresponding longitudinally to the spaces between the myofibrils and transversely to the Z regions of the myofibrils.

Effects of prazosin in patients with hypertension.

A double-blind placebo crossover trail (2 periods, each of 6 wk) was carried out in 12 patients. In the first period the patients were randomly allocated to either their individual established dose of prazosin or to the same number of placebo tablets; treatment was reversed after 6 wk. Blood pressure was higher by 17/8 mm Hgin the lying posture and by 24/14 mm Hg in the standing posture during placebo than during prazosin treatment. Standing pulse rate and body weight were higher and plasma renin activity lower during prazosin treatment. Postural hypotension occurring 1 to 2 hr after the first few doses was noted in one third of the patients when they resumed prazosin treatment after the placebo course.

Guidelines for antihypertensive therapy: problems with a strategy based on absolute cardiovascular risk.

It has been suggested that selection for antihypertensive therapy should be based on absolute risk of a cardiovascular disease (CVD) event and that treatment should be offered only if the 10-year risk exceeds 20%. Although interesting and challenging, this strategy would have the effect of greatly emphasizing treatment of the elderly and downplaying treatment of the middle-aged. It is argued in this paper that the use of one and the same time-frame for all age groups is illogical; some inverse age-related adjustment is needed. In addition, it is suggested that selection for active treatment would be better based not on the total absolute risk of CVD but rather on the marginal hypertensive risk (i.e. that part of the total risk which can be attributed to raised blood pressure). Problems in the use of antihypertensive drugs in people with 'high normal' blood pressure in order to compensate for risk factors such as obesity, hyperlipidaemia and smoking are discussed. The effect of antihypertensive treatment administered in large-scale trials to the most hypertensive control subjects has been (and continues to be) largely ignored; it should be taken into account in all calculations in this field. A policy based on absolute risk is certainly worth examining but it should not be considered self-evidently correct and needs testing in all its aspects before it is adopted on a large scale.

Handling of a salt load by hypertensive and normotensive rats on normal and low intakes of sodium.

The handling of an intraperitoneal salt (NaCl) load (about 10% of body Na) was studied by means of a whole-body counting method using 22Na in four strains of rat: spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY), New Zealand genetically hypertensive rats (GH), and outbred normotensive rats (N). The rats had previously been equilibrated so that their body Na was of the same specific activity as the injected NaCl. The load was given first at 10 weeks of age, while the rats had a choice of water and 0.5% NaCl to drink, and again at 13 weeks when the rats had a choice of water and 0.04% NaCl. All the strains excreted the load more slowly when on the low Na intake. The SHR excreted the load most quickly and the WKY most slowly. There was no difference between the GH and N rats in this respect. The SHR differed from the other strains in having an increased appetite for salt and an increased total body sodium relative to body weight.

Different associations of blood pressure with 24-hour urinary sodium excretion among pre- and post-menopausal women. WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study.

OBJECTIVE: Having found no definite relationship between blood pressure (BP) and 24h sodium excretion in women aged 48-56 years (in contrast to the results in men of the same age) in the WHO Cardiovascular Diseases and Alimentary Comparison (WHO-CARDIAC) Study, we analyzed the data to investigate whether the sodium-BP association differed between pre- and post-menopausal women. DESIGN AND METHODS: The WHO-CARDIAC is a multicenter cross-sectional study, involving, as of July 2000, 60 collaborating centers in 25 countries. In each center, 100 men and 100 women aged 48-56 years were selected randomly from the general population of the area. In this report, 2,212 women in 21 centers located in 17 countries worldwide, who had data on menopausal status, were studied. RESULTS: After adjustment for age, body mass index (BMI) and 24h urinary potassium excretion, 24h sodium excretion was positively and significantly associated with systolic blood pressure (SBP) [pooled regression coefficient: 0.037 (SE 0.01), P < 0.01] and with diastolic blood pressure (DBP) [0.023 (0.006), P< 0.01] in post-menopausal women. Pooled regression coefficients of sodium-BP association were not significant in pre-menopausal women (P< 0.05). Cross-center correlation analyses of the 21 centers showed that 24h sodium excretion was positively associated with SBP and DBP in both pre- and post-menopausal women, and this positive association between sodium excretion and SBP was significant in post-menopausal women (R2 = 0.23, P = 0.029). CONCLUSION: Different associations between sodium and BP were observed in women with pre- and post-menopausal status. There may be a tendency for salt sensitivity to increase at the menopause.

Clonidine in menopausal flushing: a double-blind trial.

Twelve hypertensive women were treated with low doses of the antihypertensive drug clonidine for their menopausal flushing in a double-blind trial. There was a high degree of placebo effect but clonidine at a daily dose of 150mug was more effective than placebo.

Licorice consumption among high school students.

A survey was carried out of licorice intake among 603 4th and 5th form pupils of two Dunedin high schools. Licorice was eaten on a regular (weekly) basis by 29 percent of the girls and 17 percent of the boys. At least 200 g (of black licorice confectionery) was eaten weekly by 5.9 percent of the girls and 4.9 percent of the boys; at least 500 g was eaten weekly by 1.8 percent of the girls and I percent of the boys. The intake reported by two pupils exceeded 1000 g per week.

Cigarettes and accelerated hypertension.

The smoking and drinking habits of 58 patients with accelerated hypertension were compared with those of a control group of 58 patients with benign hypertension, each individually matched for age, sex and date of presentation. Thirty-eight (66 percent) of the patients with accelerated hypertension were regular smokers compared to 26 (45 percent) of the control group. This excess of smokers was significant, but the average number of cigarettes smoked by smokers in the two groups was similar. The number of patients known to consume alcohol was the same in the two groups; and there were no significant differences in amount of alcohol drunk. Smoking and alcohol habits were not related. Thirty-six patients (62 percent) with accelerated hypertension had serum creatinine levels greater than 0.12 mmol/l compared with nine (16 percent) of the control group. Seventeen (29 percent) patients with accelerated hypertension were known to have died compared with five (9 percent) of the control group. This survey confirms that, as shown by recent studies in Britain, smoking is more common in patients presenting with accelerated than with benign hypertension. It appears that hypertensive patients who smoke regularly are more likely to develop the accelerated phase than those who do not.

Alcohol consumption and blood pressure in a New Zealand community study.

The relationship between stated alcohol consumption and blood pressure was investigated in 901 adults who participated in a multiphasic health survey in Milton in May 1981. Subjects taking oral contraceptives or drugs which could lower blood pressure were excluded. Eighty-five percent of men and 52% of women reported taking some alcohol at least once a month. The percentage using alcohol was highest (96%) in men aged 20-29 years. The reported mean weekly intake by users was 171 g for men and 56 g for women. After adjustment for age and body mass index, there was a positive association between alcohol intake and blood pressure for men. The mean systolic and diastolic pressures of male heavy alcohol users (300 g or more alcohol per week) were, respectively, 9.8 and 8.9 mmHg higher than those of male non-drinkers. No relationship between alcohol intake and blood pressure was found in the women.

A questionnaire survey of symptoms in a hypertension clinic.

OBJECTIVE: to assess symptoms of patients on antihypertensive therapy. SETTING: hospital hypertension clinic. DESIGN: self administered questionnaire (sent and returned by mail) listing 23 symptoms; four grades of response (none, mild or seldom, moderate or sometimes, severe or frequent); special scale for nocturia and appetite. PATIENTS: 302 patients completed the questionnaire (87% of those to whom it was sent); 109 of these patients completed it a second time, after an interval of four months, so that repeatability could be assessed. REPEATABILITY: scores were high, ranging from 0.92 to 0.99, for all symptoms except flushing (all grades 0.91), nausea (all grades 0.90) and sleepiness (severe, 0.82) (method of Bulpitt et al). RESULTS: overall prevalence of symptoms was high, but most were mild or infrequent. Women had significantly greater prevalence of oedema, flushing and insomnia than men and tended to assess their symptoms more often as severe or frequent. Nocturia was the only symptom more common in those above median age (62 yr) than in those below. Lack of energy was the only symptom more prevalent in the treated than in the untreated. No difference in prevalence of symptoms was detected between those taking or not taking a specific type of drug (beta blocker, diuretic, ACE inhibitor, calcium antagonist). CONCLUSION: in patients whose antihypertensive therapy has been carefully adjusted to try to avoid symptomatic side effects, the burden of such side effects appears to be very small.

Iodide excretion in a salt-restriction trial.

Twenty-four hour urinary iodide excretion was measured twice, with a four month interval, in 133 individuals who were in a 12-month salt-restriction study in an area where iodine-deficiency goitre was once common and where most household salt is iodised. Half the subjects were salt restricted; their mean 24 h sodium excretion after eight months was 89 mmol for men and 73 mmol for women. Iodide excretion correlated with sodium excretion in the whole group on each occasion. After eight months mean 24 h iodide excretion in the salt-restricted group (men 1.3 SD 0.6 mumol, women 1.1 SD 0.4 mumol) was lower (p less than 0.01) than that in the control group (men 1.8 SD 0.8 mumol, women 1.7 SD 0.8 mumol), but was reasonable in terms of recommended dietary allowances (1.2 mumol, 150 mg). Mean iodide content of local milk was 1.3 mumol/l. Any salt that is used in the home should continue to be iodised. However, it has become unnecessary in this population to use salt (ie, iodised salt) simply in order to avoid iodine deficiency, so long as other foodstuffs continue to contain iodine as at present. As the other sources of iodine may be subject to change, the adequacy of intake of iodine from these sources should be monitored from time to time in samples of the population.

What do middle-aged New Zealanders eat? A dietary survey in 50-54 year olds in south Canterbury and north Otago.

Information on diet was obtained from a random sample of 50-54 year olds in October 1985 when a health survey was conducted in the Timaru health district. This survey formed part of the international cardiovascular diseases and alimentary comparison (CARDIAC) study. A seven-day dietary history was obtained from 99 male and 82 female participants who were not taking any antidiabetic or antihypertensive medication. The median daily energy intake was 10.5 MJ for the men and 6.3 MJ for the women. The median daily total fat intake for men and women respectively was 103 g and 68 g. The median ratio of polyunsaturated to saturated fatty acids was low, 0.19 for the men and 0.18 for the women. Total fat contributed 37.5% to energy intake of men and 38.5% to energy intake of women and alcohol contributed 5.1% for men and 2.1% for women. Mineral and vitamin intakes were generally satisfactory. A substantial proportion of the participants, particularly women, claimed to have decreased their total food, fat, salt, meat, eggs and milk intakes and to have increased their vegetable and fish consumption.

Age, adiposity, blood pressure and blood lipids in a rural New Zealand population.

Multiple regression analysis of data on age, blood pressure, adiposity and blood lipids from a rural New Zealand population of over 1200 adults has been undertaken. The results show that rises in blood lipids over time in the population are independent of age and correlate significantly with adiposity. Thus plasma cholesterol and triglycerides correlate with adiposity (expressed as Quetelet's index or skinfold thickness) in men whereas significant correlation in women was only between adiposity and plasma triglycerides. Systolic and diastolic blood pressure in men was strongly correlated with their plasma triglycerides, but not cholesterol, when the effect of age and adiposity was removed. In women however only a weak correlation was observed between plasma triglycerides and systolic blood pressure. The significance of the findings is discussed.

Treatment of hypertension with labetalol.

Labetalol, a new antihypertensive drug which combines alpha- and beta-blocking properties, was used in an open clinical trial in a mixed group of 47 adult patients with mainly essential hypertension, many of whom had been poorly controlled on other drugs. Labetalol lowered lying and standing blood pressures significantly when given alone or when combined with other antihypertensive drugs and it was generally well tolerated. It is easy to use, and in some severe cases has been dramatically effective. Mean daily dose was 767 mg. A postural hypotensive effect was seen especially in patients taking concomitant diuretics but was not troublesome. Labetalol reduced heart rate in patients who were not on previous or concomitant beta-blocker therapy. Side effects were few and did not cause major problems. A transiently or persistently weakly positive ANF was noted in nine patients; the significance of this is uncertain at this stage and needs further assessment. Raynaud's phenomenon, which had complicated previous beta-blocker therapy in some patients, improved with labetalol.

The Milton Survey. 2. Blood pressure and heart rate.

Blood pressure and heart rate were measured in 1,206 adult inhabitants of Milton, about 82 percent of the adult population. Mean blood pressure for the various 10 year age groups was very similar to that found in other comparable societies. There was quite a high prevalence of blood pressure levels of 160/95 mmHg or over, especially in the older age groups. Blood pressure was lower in young women than in young men but rose more steeply with age in women than in men, so that in old age it was higher in women than men even though antihypertensive treatment was much more common in the women. Heart rate was higher in women than in men; in both sexes, heart rate correlated strongly with blood pressure. Quetelet's index (weight/height) also correlated strongly with blood pressure; this suggests once again that the amount of hypertension in the community might be reduced if body weight could be kept at desirable levels.

A pilot study to test the feasibility of salt restriction in a community.

Index subjects were selected from the population of Milton studied in the May 1981 survey. Index subjects aged 64 or less with a systolic blood pressure 138-179 mmHg (18.35/23.8 kPa), including those on antihypertensive treatment, were invited to participate with their families. Index subjects were divided into two matched groups. One group was randomly assigned to be the control group and the other to be the salt-restriction group. Age, weight, height and 24-hour urinary excretion of sodium, potassium and creatinine at the start of the study in August 1981 were similar for the control and salt-restriction groups. When tested in November 1981, the salt-restriction group had achieved a reduction in 24-hour sodium excretion to a mean of 84 mmol for men and 70 mmol for women; corresponding values for the control groups were 150 and 120 mmol. A further test in March 1982 showed little further change. Potassium output changed very little. Attitudes to the low-salt diet varied, but 87 percent found it tolerable or actually preferable. There is no doubt that major reductions in sodium intake are feasible. However, if these are to be achieved on a large scale, food, manufacturers will need to offer a variety of low-sodium foods.

Selenium and risk factors for cardiovascular disease in New Zealand.

Blood selenium (Se) concentrations and glutathione peroxidase (GSHPX) activities were measured in 118 men (39 +/- SD 15 yr) and 112 women (42 +/- 16 yr) randomly selected from the total respondents (1192) to health survey in Milton, a low soil-selenium area in Otago. GSHPx activities were marginally lower for men (11.9 +/- 3.2 units/g Hb) than for women (12.9 +/- 3.8 units/g Hb). Blood, erythrocyte and plasma selenium concentrations were about the same for both sexes and means for all subjects (61 +/- 15; 73 +/- 19; 49 +/- 12 ng Se/ml) were almost identical with a control group of Otago blood donors. No differences in blood levels could be associated with smoking, use of oral contraceptives, arthritis and/or rheumatism, or anti-hypertensive drugs. No relationship was found for the men or women between any of the parameters of selenium status and any of the parameters of risk factors for cardiovascular disease measured in the health survey: age, Quetelet's index, total skinfolds, systolic and diastolic pressure, pulse rate, plasma lipids and lipoprotein lipid concentrations. Moreover no relationship was found for the subgroups (36% group) of men and of women with plasma selenium below 45 ng Se/ml. This study indicates that if selenium is important it does not operate through the risk factors of cardiovascular disease as presently understood.