Lower Mean Blood Pressure Research Articles

Effects of timolol and propranolol on inducible sustained ventricular tachyarrhythmias in dogs with subacute myocardial infarction

Timolol and propranolol reduce the incidence of cardiac death after myocardial infarction (MI). To explore possible mechanisms of this reduction in mortality, the antiarrhythmic effects of these 2β blockers were compared in a dog model of inducible sustained ventricular tachycardia (VT) or fibrillation (VF) 4 to 6 days after experimental closed-chest MI. Dogs with inducible VT or VF underwent drug studies with timolol and propranolol; the sequence of drug administration was randomized. Timolol doses were 0.1, 0.3, and 1.0 mg/kg; propranolol doses were 1.0, 3.0 and 10.0 mg/kg. Timolol and propranolol were equally effective in abolishing inducible VT or VF: 77 % of instances of inducible VT or VF responded to 1 or bothβ blockers. The VF threshold was significantly elevated by both timolol and propranolol; the elevation in the VF threshold was significantly greater in “responders,” i.e., dogs in whom VT was prevented by p blockade (15±9vs8±9 mA, p < 0.05). The ventricular effective refractory period was prolonged by both drugs; again, more so in the responders than in the nonresponders (16 ± 9 vs 8 ± 14 mA, p < 0.05). The QTc interval was not significantly affected by eitherβ blocker. Among the responders, no difference was detected between timolol and propranolol in the extent to which the effective refractory period was prolonged or the VF threshold elevated. However, the highest dose of propranolol decreased the mean blood pressure significantly more than the comparable dose of timolol. In conclusion, timolol and propranolol are equally effective in abolishing inducible VT or VF in the dog after subacute MI. Both drugs tend to elevate the VF threshold and to prolong the ventricular effective refractory period without significantly altering the QTc interval, suggesting a possible direct membrane depressant effect for both drugs. At a high dose, propranolol tends to lower mean blood pressure more than the comparable dose of timolol.

Effects of captopril on vascular noradrenergic transmission during the development of two-kidney, one clip Goldblatt hypertension in rats.

Vascular noradrenergic transmission and the effect of captopril on this transmission were examined in the blood perfused rat mesenteric vasculature in situ during the development of two-kidney, one clip Goldblatt hypertension. Three groups of rats including sham operated, 6-8 day hypertensive and 4-6 week hypertensive were studied. Mean blood pressures during anaesthesia were 90.0 +/- 2.0, 119.7 +/- 4.7 and 131.8 +/- 6.8 mmHg in the three groups, respectively. Mesenteric vasoconstrictor responses to norepinephrine were significantly potentiated in both of the hypertensive groups relative to the sham group. Mesenteric vasoconstrictor responses to nerve stimulation were similar in the sham and 6-8 day hypertensive groups. However, responses to nerve stimulation were significantly potentiated in the 4-6 week hypertensive group relative to the sham group. Captopril (1 mg/kg, i.v.) lowered mean blood pressure in all groups, equalizing blood pressure in the 6-8 day hypertensive and sham groups. However, the blood pressure in the 4-6 week hypertensive rats remained significantly elevated after 1 mg/kg captopril. An additional dose of captopril did not lower blood pressure further in this group. Mesenteric vasoconstrictor responses to nerve stimulation and norepinephrine in the three groups were minimally affected by captopril, with significant differences between control and captopril-treated responses occurring randomly at a point or two in a dose-response or frequency-response curve for a given group. The differences in vascular responsiveness to nerve stimulation and norepinephrine between the hypertensive and sham groups continued to be evident after captopril.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiopulmonary toxicity in patients with breast carcinoma during plasma perfusion over immobilized protein A: Pathophysiology of reaction and attenuating methods

Tumoricidal reactions in dogs with spontaneous breast carcinoma occur after perfusion of plasma over protein A derived from Staphylococcus aureus and immobilized in collodion charcoal. When this treatment was extended to humans with breast cancer, heniodynamic and physiologic changes were noted. The evolution and spectrum of these reactions were evaluated during 47 plasma infusions in five patients. Initial treatment conditions consisting of rapid perfusion of plasma over high quantities of immobilized protein A were employed for 12 treatments in two patients. Within 30 minutes after treatments were begun, mean blood pressure, systemic vascular resistance, and stroke volume increased, as did heart rate, cardiac output, and rectal temperature; however, mean pulmonary artery pressure and total pulmonary resistance did not change. At 90 minutes, hypotension developed (lowest mean blood pressure was 59 ± 14 mm Hg) that was associated with a decrease in systemic vascular resistance and total pulmonary resistance (536 ± 66 and 146 ± 44 dynes·second·cm −5, respectively). Cardiac output increased, tachycardia developed, stroke volume decreased, and rectal temperature increased. During the hypotensive phase, values of creatinine clearance and fractional excretion of sodium diminished. Noncardiogenic pulmonary edema appeared occasionally, with bronchospasm noted once. No hemodynamic changes were seen when saline solution was passaged over protein A immobilized in collodion charcoal or when autologous plasma was given without passage over protein A immobilized in collodion charcoal. Treatment conditions were modified by diminishing protein A quantity and plasma volume and slowing plasma perfusion rate, which resulted in significant attenuation of all cardiopulmonary responses. This report, then, defines for the first time the physiologic basis of the cardiopulmonary toxicity in humans after plasma perfusion over immobilized protein A.

Hemodynamic Consequences of Abrupt Withdrawal of Nitroprusside or Nitroglycerin Following Induced Hypotension

Nitroprusside (SNP) and nitroglycerin (TNG) are frequently used to control or reduce blood pressure during anesthesia and are reported to produce similar hemodynamic changes during infusion. However, few data are available concerning the cardiovascular changes following abrupt withdrawal of these drugs. In this study, two groups of five dogs, each anesthetized with halothane, received either SNP or TNG in amounts sufficient to reduce mean arterial blood pressure to 30% below control levels. Both groups were maintained at this level for 30 minutes, the drugs then being abruptly discontinued. Hemodynamic measurements were then repeated intermittently for an additional 120 minutes. Both groups demonstrated generally similar responses during the hypotensive period although cardiac output increased by 28% in the dogs given TNG but did not change in those given SNP. During recovery, however, mean blood pressure rapidly returned toward normal in dogs given SNP, but mean pulmonary arterial pressure increased 24% above control levels, and remained elevated. In contrast, dogs given TNG had a markedly slower recovery phase, with more than 2 hours required for mean blood pressure to approach control values. During this time, mean pulmonary arterial pressures never exceeded control levels. An attempt was made to correlate these changes with circulating plasma catecholamine levels. During drug infusion, both epinephrine and norepinephrine levels increased at least transiently. After SNP was stopped, both epinephrine and norepinephrine levels rapidly returned to control levels. By contrast, plasma norepinephrine levels remained significantly above normal in animals that had received TNG, in spite of persistently low mean blood pressure and mean pulmonary arterial pressure. These data indicate that the period following discontinuation of SNP or TNG is accompanied by very different hemodynamic changes, and that abrupt discontinuation of SNP, but not TNG, produces a rebound pulmonary hypertension unrelated to plasma levels of catecholamines. By contrast, prolonged vasodilation was noted after TNG. Therefore, these drugs are clearly not identical, and differences following discontinuation should be considered when choosing an agent for producing controlled hypotension.

Evidence from a dual action of converting enzyme inhibitor on blood pressure in normal man

We studied the effect of a converting enzyme inhibitor (CEI), Captopril SQ 14,225 50 mg p.o. in eight supine normal subjects under a high sodium (150 meq/d) and low sodium (25 mEq/d) diet. On high sodium, plasma renin (PRA) and aldosterone were basal and Saralasin did not lower mean blood pressure. However, CEI induced an 11.4±3.2 mm fall in blood pressure (p<0.02) and either indomethacin 50 mg or ibuprofen 800 mg (PI), when given simultaneously on another day, abolished the blood pressure response (2.5±0.9 mm Hg, p>0.5). In contrast, on a low salt diet where renin was increased, CEI induced a drop in blood pressure which was not significantly altered by PI (12.8±1.1 vs. 10.0±3.1 mm Hg, p>0.5). CEI increased plasma renin on both diets (1.7±0.5 to 3.5±0.8 and 2.8±0.6 to 12.5±3.1 ng/ml/hr respectively both p<0.05). Aldosterone did not change (high Na +) or fell (low Na +). Inhibition of prostaglandin synthesis did not significantly block the renin rise from CEI suggesting that the direct angiotensin II negative feedback is relatively independent of acute prostaglandin release. Our studies suggest that CEI has a dual hypotensive action. In a low renin state, the hypotensive action appears to be mediated through vascular prostaglandins.

Sodium and potassium intake and blood pressure.

Sodium and potassium intakes were increased in normotensive volunteers to assess the effects on their blood pressures. An approximately threefold increase in sodium intake for eight days had no effect on the blood pressures of seven volunteers, while a two-stage increase in potassium intake, by about 40% for eight days and a further 55% for 14 days, had no effect on the blood pressures of 21 volunteers. Renal electrolyte excretions and the blood pressures of all 28 subjects showed no statistically significant correlations between either sodium or potassium excretion and blood pressure. A weak negative correlation was found between the sodium: potassium ratio and systolic pressure. The small reductions in sodium intake and increases in potassium intake that might be achieved through propaganda and changes in food processing are unlikely to lower mean blood pressure in Western societies.

BLOOD PRESSURE PERCENTILE CHARTS IN AUSTRALIAN SCHOOL CHILDREN

Blood pressures (BP) were measured in 3,000 school children aged between 7 & 13 years in the Adelaide metropolitan area. Schools cover wide socio-economic groups. All measurements were by one nurse at schools using a London School of Hygiene Blind Reading Sphygmomanometer. Each child had BP measured sitting. The first reading was taken as soon as practical after the child had been seated. Subsequent readings were 5 & 10 minutes later. First, 4th & 5th sounds were recorded. Each child had a cuff that totally encircled the upper arm and was the maximum width that would fit. Mean BP at the initial recording ranged from 98/58/55 at 7 to 118/70/68 at 13. At 5 minutes the range was 95/58/56 at 7 to 113/70/68 at 13, and at 10 minutes 90/55/54 at 7 to 108/67/65 at 13. There was a steady rise in all BP recordings with age. In each age group there was a consistent fall from zero time to 10 minutes. This was more pronounced with systolic than diastolic readings. At all ages there was a small difference in BP between boys and girls - boys being consistently higher. Adequate percentile charts for BP in Australian children have not previously existed. Our figures show lower mean BP than studies in North American children, stressing importance of such studies in individual populations. Recording of readings at 5 & 10 minutes are useful in the overall assessment of BP in children.

Effects of dietary sodium and sucrose on the induction of hypertension in spider monkeys

Since excessive salt (NaCI) intake and its interaction with dietary carbohydrates are considered possible etiological factors in the genesis of human essential hypertension, three groups of spider monkeys (Ateles Sp.), six in each group, were fed chow-based diets containing no added NaC1 (control),3% NaC1 (9.9 mg/kcal) or 3% NaC1 and sucrose at 38% of calories.Systolic and diastolic blood pressure (BP). weights, Na�, K�, creatinine, cholesterol, triglycerides, and lipoproteins (LP) were measured during 3 weeks of basal and 8 weeks of experimental periods. The mean (±2 SE) systolic/diastolic BP for control, NaCI, and NaC1-sucrose were 141.9 ± 2.4/96.0 ± 2.2 mm Hg, 163.0 ± 5.2/108.2 ± 1.7 mm Hg, and 165.8 ± 5.2/108.4 ± 3.0 mm Hg, respectively. There were significant differences in BP (P < 0.0005), serum Na� (P < 0.025), K�(P < 0.05), and triglycerides (P < 0.025) between control and experimental groups. Compared to NaCI group, NaCI-sucrose group had significantly higher rise in systolic and diastolic BP, indicating a poten- tiating effect of sucrose on the salt-induced hypertension. Similarly, NaCI-sucrose had higher serum cholesterol, $-LP, a-LP, and Naand lower Kcompared to the NaC1 group. Both systolic and diastolic BP correlated positively with body weight and negatively with serum Kand triglycerides. Body weight correlated positively with serum Na�, creatinine and pre-f�-LP and negatively with serum K�. That the monkeys with high or low initial mean BP levels remained more or less in the same order during the experimental dietary period suggests the concept of genetic proneness and tracking. Although these studies cover a short period of observation, the synergistic effect of dietary sodium and sucrose on the induction of hypertension in this nonhuman primate species has a potentially important bearing on human hypertension. Am. J. Clin. Nutr. 33: 561-569, 1980.

Dietary fibre and blood pressure.

Ninety-four volunteers participated in a three-day weighed dietary survey and had their blood pressures measured once. They were classified according to their fibre intake. Subjects with a high-fibre intake were found to have lower mean blood pressures than those with a low-fibre intake. Forty-two of the volunteers further participated in a group of experiments. Those eating a high-fibre diet decreased their dietary fibre, and those eating a low-fibre diet increased their dietary fibre. The first group (11 subjects) showed increased mean blood pressures after four weeks of eating the experimental diet. The last group (31 subjects) showed decreased mean blood pressures after four weeks of eating the experimental diet. The 11 subjects consuming the low-fibre experimental diet showed a decrease in mean blood pressure when some of the saturated fat in their diet was replaced by polyunsaturated fat. A similar substitution carried out by 14 of the subjects consuming the high-fibre experimental diet also resulted in decreased mean blood pressure, but this was not statistically significant. Twelve more volunteers, with hypertension, were all found to have low-fibre diets. They consumed a high-fibre diet for a six-week experimental period, but their mean blood pressures did not decrease significantly; individual recordings varied substantially during this period.It is suggested that differences in the type and quantity of dietary fibre and fat may be responsible for the lower mean blood pressures of groups of vegetarians compared with similar groups of non-vegetarians.

Comparison of hemodynamic effects of exercise and isoproterenol infusion in normal young and old men.

Hemodynamic comparison of ergometer exercise with isoproterenol infusion was carried out in normal young and old men, and age associated difference in responses to exercise and isoproterenol was evaluated. Ergometer exercises of 50, 100 and 150 W in young men, averaging 23.0 years, increased heart rate in linear fashion from 73.8 to 149.2, while stroke index was raised at 50 W and remained at the same level thereafter. The isoproterenol infusion of 0.02 and 0.04 microgram/kg/min increased heart rate, stroke index and cardiac index by similar amount to 50 and 100 W or ergometer exercise respectively. Ergometer exercise elevated systolic, diastolic and mean blood pressure linearly, while isoproterenol infusion lowered diastolic and mean blood pressure. In old men, averaging 73.0 years, the tolerable limit of ergometer exercise was 40 W. The increases in heart rate, cardiac index and blood pressure at the comparable work level were by similar amount to the young subjects, indicating the identical hemodynamic responses in young and old men at the same work load. Cardiac index to isoproterenol infusion of 0.02 microgram/kg/min showed less increase than ergometer exercise of 40 W in the aged. Furthermore, the increase in cardiac index to isoproterenol was less in old than young men, showing a decreased response to beta adrenergic stimulation in the aged.

Capillary size and density in the cerebral cortex of rats with a porto-caval anastomosis.

Morphometric investigation by automatic image analysis of alkaline phosphatase positive brain capillaries was performed in control rats and in rats with a 30 days old porto-caval anastomosis. Rats with a porto-caval anastomosis showed an increased capillary diameter Di and as a consequence of this a decreased capillary surface-to-volume ratio Si/Vi. The free capillary distance was increased and the capillary length per unit brain volume LVi was decreased in the shunted rats compared to the controls. There was no difference in the percentage of the projected capillary area AAi% between the two groups. It is suggested that the dilatation of the capillaries in rats with a porto-caval anastomosis is caused by the altered haemodynamic properteries with a low mean blood pressure although the cardiac output is increased and that the alteration in free capillary distance and length per unit brain volume LVi is caused by dispersion by cortical edema induced by the porto-caval anastomosis.

A mathematical model of aging processes. IV. A multivariate analysis of blood pressure in a Montreal and a Utah population.

Two populations, one Montreal- and one Utah-based, were studied with respect to heart disease risk factors on a cross-sectional basis. The Utah population afforded consistently lower mean blood pressures than the Montreal population, although there was not evidence that the Utah population was less obese, or had a lower pulse rate. Also, in the Utah population, it was found that the proportion of persons with a family history of heart disease did not differ significantly in the hyper- and normo-tensive groups. Fourteen parameters were investigated in the Montreal population, and the analyses indicated that, when other variables are controlled, age, pulse rate, some measure of serum lipid levels, and a family history of heart disease generally assist in the discrimination between the hyper- and normo-tensive groups, but the obesity measurement did not. In that sense, obesity, on its own, may not be considered a risk factor for hypertension.

Study of coronary risk factors related to physical activity in 15 171 men.

Physical activity, both at work and during leisure, was assessed in 15 171 men aged 25-74 years. Heavy leisure activity was associated with lower mean serum cholesterol levels and blood pressure. In men under 60 years the same negative association was also noted between leisure activity and relative weight and cigarette smoking. Different degrees of physical activity at work were not associated with any differences in these risk factors, nor did the level of exercise at work seem to influence the negative association between leisure activity and risk factors. Heavy leisure activity in young and middle-aged men is associated with lower levels of certain coronary risk factors and, therefore, a lower risk of coronary heart disease. The often-reported reduction in coronary morbidity and mortality with physical exercise may not be the direct effect of the exercise itself.

The effect of pair-feeding on blood pressure and growth in young-adult female rats with ventromedial hypothalamic lesions.

Sixty day old Holtzman rats received electrolytic lesions in the ventromedial hypothalamic nuclei. One group of rats was pair-fed with sham-operated controls, a second group of lesioned rats was allowed to eat “ad libitum”. Blood pressure and body weight and length were measured weekly for four weeks after which time the animals were sacrificed. Pair-fed rats with lesions, despite a sodium intake identical with that of the controls, showed a significantly lower mean terminal blood pressure. On the other hand, lesioned rats fed “ad libitum” had a terminal blood pressure almost identical with that of the controls but ate significantly more sodium than intact controls and the lesioned pair-fed rats. Growth as assessed by body length, tail length and pituitary acidophil count was reduced equally in both lesioned groups. Relative weights of pituitary, adrenals, thyroid and ovaries were smaller in the “ad libitum”-fed rats than in the pair-fed animals which in turn had smaller organs than the controls. The thyroids showed no gross changes from the normal. The data suggest that ventromedial lesions in young-adult rats cause a disruption of the neuroendocrine milieu as they do in weanling rats. Howeve, the increased sodium intake accompanying hypothalamic hyperphagia appears to maintain blood pressure in the range of control rats. When sodium intake of lesioned rats is kept the same as that of unlesioned animals the blood pressure actually falls. Thus, ventromedial lesions in both weanling and young-adult rats produce a fall in blood pressure which is masked, apparently, in the adult rats by the increased sodium consumption incident to the accompanying hyperphagia in the adult animals. The mechanism of this hypotensive effect of ventromedial lesions is not known.

EFFECT OF TIME OF REDUCTION OF RENAL MASS ON DEVELOPMENT OF ADRENAL-REGENERATION HYPERTENSION.

Summary1. Salt-treated, uninephrecto-mized-adrenalectomized and contralaterally adrenal enucleated female rats in which those operative steps are performed shortly after weaning (zero time) show a higher mean terminal blood pressure and greater enlargement of heart, kidney, brain and spleen than do similar rats that are operated on 2 weeks after zero time. 2. Performance of the uni-nephrectomy 2 weeks after uniadrenalectomy and adrenal enucleation results in significantly lower terminal mean blood pressure and correspondingly lower lesion severity indices. This suggests that the enucleation step proper is the crucial operation in bringing about the full severity of the hypertensive syndrome. 3. Uninephrectomy and uniadrenalectomy on day zero and contralateral enucleation of the compensatorily-hypertrophied adrenal 2 weeks later results in mean terminal blood pressure and lesion severity indices comparable to those rats in which these operations are carried out at zero time. Blood pressure only rises steep...