BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake.

A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction.

Inhibition of furosemide-induced increases in plasma renin activity by amiloride.

The effect of the potassium-sparing diuretic, amiloride, was studied in conscious rabbits bearing chronic indwelling cannulas to assess whether its reported in vitro kallikrein-inhibiting activity may produce a suppressive effect on furosemide-induced renin secretion similar to that previously demonstrated with another kallikrein inhibitor, aprotinin. Furosemide elicited a rapid and persistent rise in plasma renin activity (PRA), but pretreatment of the same rabbits with a 15-minute intravenous infusion of amiloride, which amounted to 1 mg/kg and commenced at 30 minutes before furosemide, completely prevented this rise. Amiloride also prevented furosemide-induced kaliuresis without an attenuation of the diuretic or natriuretic response and did not alter plasma potassium concentration in the absence of any change in external potassium balance, indicating that suppression of the PRA response is due neither to prevention of extracellular fluid volume contraction nor to the known suppressive effect of hyperkalemia. Mean arterial pressure tended to fall slightly but not significantly with or without amiloride pretreatment. On the basis of these findings and those of our antecedent study with aprotinin, we conclude that the striking similarity between the suppressive effects of two dissimilar inhibitors of kallikrein on pharmacologically evoked renin secretion is consistent with the hypothesis that renal kallikrein participates in the mechanism of renin secretion in vivo.

Hypertension associated with hyperparathyroidism is not responsive to angiotensin blockade.

Patients with primary hyperparathyroidism are frequently hypertensive. Studies were performed to determine whether the hypertension in this disorder could be corrected by saralasin infusion. Five patients with primary hyperparathyroidism and one patient with secondary hyperparathyroidism were salt depleted before saralasin testing by the administration of 1 mg/kg furosemide at 1700 h on the evening before testing. Blood pressure was measured every 2 min by an automatic recording device. Saralasin was given as a continuous iv infusion of 1, 3, 6, and 10 micrograms/kg . min for 30 min. Blood for measurement of PRA was drawn 4 min before, immediately before, and 4, 8, 12, 16, 22, 30, 60, and 90 min after the infusion was begun. Saralasin did not reduce blood pressure in these patients. The mean postsaralasin blood pressure (12--20 min after the start of the infusion) was 155/102 mm Hg compared to the control blood pressure of 156/101 mm Hg (blood pressure at -4 and 0 min). The inability of saralasin to effect a vasodepressor response was unexpected, since the mean PRA before saralasin infusion was elevated at 1895 ng/dl . 3 h (normal range, 409--818 ng/dl . 3 hr; 95% confidence limits). These studies suggest that the hypertension associated with hyperparathyroidism is not renin dependent.

The effect of weight loss on reproductive hormones in obese men.

The effects of weight reduction on reproductive hormones were investigated in 24 moderately obese men, 18-108% above ideal body weight. Serum estrone (E1), estradiol (E2), testosterone (T), percent free T (%FT), sex hormone binding globulin (SHBG) capacity, and, in 9 subjects, androstenedione (A) were measured serially before and during an outpatient supplemented fasting program (320 kcal/day) for 8-20 weeks. In the baseline state mean E1 was elevated to 100 +/- 7 pg/ml (normal, 30-60 pg/ml). The E2 was slightly elevated to 36 +/- 3 pg/ml (normal, 8-35 pg/ml). The mean T of 400 +/- 20 ng/dl was at the lower end of normal (400-1000 ng/dl). The mean %FT was elevated to 4.1 +/- 0.2% (normal 1.6-3%). The calculated free T was normal. The mean SHBG binding capacity was 0.99 +/- 0.05 micrograms dihydrotestosterone bound/dl (normal, 1.0-1.8 micrograms/dl). The mean A of 52 +/- 5.8 ng/dl was normal. These data were in accord with previous findings in much heavier men. Eight weeks of weight loss (mean, 19.5 kg) were associated with normalization of all the measured parameters. The mean E1 decreased to 48 +/- 23 pg/ml, E2 to 28 +/- 2.1 pg/ml. T increased to 536 +/- 35 pg/dl and %FT fell to 3.2 +/- 0.2%. Data on men remaining on the program for 16 or 20 weeks showed a continued fall of estrogens and stabilization of T and %FT. SHBG and A did not change significantly over the entire time period. In conclusion, increased circulating estrogens and reduced androgen binding were found in moderately obese men, which were completely corrected with weight loss.

Erythrocyte Na+,K+ cotransport and Na+,K+ pump in black and caucasian hypertensive patients.

Alterations in red blood cell (RBC) Na+,K+ pump and in Na+,K+ cotransport (CoT) have been described in essential hypertension (EH). We examined pump and CoT in 50 normotensive (NT) subjects and 58 EH subjects subdivided by race and family history of hypertension (+ FH). RBCs were preloaded with Na+ to obtain intracellular levels of 25 mM/liter cells by using the p-chloromercuribenzene sulfonic acid (pCMBS) method. Na+ and K+ efflux rates into a magnesium-sucrose medium were quantitated in the presence of ouabain and ouabain plus furosemide to define pump and CoT activity respectively. Mean intracellular Na+ content was higher (p less than 0.05) in black NT and HT subjects compared to Caucasians. Mean RBC CoT was lower in black EH compared to NT and compared to Caucasian NT and HT subjects. Conversely, Caucasian HT patients had higher mean CoT than NT subjects. Subdivision into + FH revealed very little effect of + FH on CoT in black NT and HT subjects. In Caucasian NT and HT subjects with + FH, mean CoT was significantly reduced (less than 0.3 mM/liter cells/hr) compared to those without + FH. A subgroup of Caucasian EH subjects displayed high CoT (greater than 0.6 mM/liter cells/hr); a + FH had little impact on the high CoT group. There was no correlation between RBC CoT activity and age, sex, severity of hypertension, urinary sodium excretion, and plasma aldosterone. There was a positive correlation (r = + 0.47; p less than 0.01) between CoT and upright plasma renin activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood pressure lowering and potassium conservation by triamterene-hydrochlorothiazide and amiloride-hydrochlorothiazide in hypertension.

Effects of once-daily doses of 50 mg triamterene with 25 mg hydrochlorothiazide and 5 mg amiloride with 50 mg hydrochlorothiazide were compared in a randomized, multicenter study of 84 adult subjects with mild to moderate hypertension (diastolic blood pressure 90 to 114 mm Hg). After a 3-wk placebo lead-in period, the subjects entered a 6-wk treatment period. The two drug regimens were compared with respect to antihypertensive effects and effects on serum potassium and magnesium levels during the final week of drug therapy, with the use of the last week of placebo therapy as a covariate. Both drug regimens substantially reduced mean supine systolic and diastolic blood pressures to well within normal limits; there was no significant difference the two groups. Twenty-four of the 41 subjects receiving triamterene-hydrochlorothiazide (59%) and 29 of the 43 patients receiving amiloride-hydrochlorothiazide (67%) had diastolic blood pressure less than 90 mm Hg at week 9. Five subjects receiving amiloride-hydrochlorothiazide (12%) and two subjects receiving triamterene-hydrochlorothiazide (5%) had hypokalemia (serum potassium level less than 3.5 mEq/l) at week 9. The average decrease in serum potassium levels during amiloride-hydrochlorothiazide therapy (-0.33 +/- 0.08 mEq/l) was greater than that after triamterene-hydrochlorothiazide (- 0.08 +/- 0.07 mEq/l). Serum magnesium levels were not changed by either regimen. Weight loss was greater in the amiloride-hydrochlorothiazide group than in the triamterene-hydrochlorothiazide group.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical detection of sarcopenic obesity by bioelectrical impedance analysis.

To assess whether bioelectrical impedance analysis (BIA) provides clinically useful information on body composition beyond that obtained from measuring height and weight, we clinically classified 306 obese patients (233 females and 73 males) into tertiles of increasing fat-free mass estimated by BIA. Because fat-free mass by BIA is an estimate of lean body mass, the lowest tertile was clinically defined as sarcopenic obesity (reduced lean body mass), as contrasted with proportionate or muscular obesity in the next two tertiles. Fat mass in patients in each of the above tertiles based on BIA was then compared with fat mass estimated by using the equations of Garrow and Webster with body mass index (weight/height2). BIA-estimated fat mass was 4.3 kg greater in the sarcopenic group (n = 102) than predicted from body mass index. Fat mass predicted by BIA in the proportionate (n = 102) and muscular (n = 102) groups differed by less than the SEE of fat mass predicted by BMI. In premenopausal women at increased risk of breast cancer BIA showed a high prevalence of sarcopenic obesity (28/30) in these women at normal body mass indexes. Thus, BIA may be clinically useful for demonstrating sarcopenic obesity, but additional studies are needed to determine the metabolic and clinical significance of sarcopenic obesity.

Efficacy and safety of triamterene/hydrochlorothiazide combinations in mild systemic hypertension.

After a 3-week placebo lead-in (Period 1), 78 patients with sitting diastolic blood pressures (BPs) of greater than or equal to 90 and less than or equal to 105 mm Hg entered a 4-week period (Period 2) during which they received triamterene (TMT) 37.5 mg/hydrochlorothiazide (HCTZ) 25 mg/day. Four weeks of therapy with TMT 37.5 mg/HCTZ 25 mg resulted in a statistically significant decrease in mean BP of -15.0/-9.6 mm Hg. Mean BP changed from 145/95 to 130/85 mm Hg. Fifty-nine percent of patients were classified as responders as defined by study criteria. An additional 4 weeks of therapy (Period 3) for responders produced no further change in BP. Nonresponders as a group continued to have a further decrease in BP in Period 3. However, only patients in whom therapy was transferred to TMT 75 mg/HCTZ 50 mg had a statistically significant decrease. All patients who changed to the higher dose combination achieved goal BP by the end of the study. Of the nonresponders who continued to take TMT 37.5 mg/HCTZ 25 mg, 69% achieved goal diastolic BP by the end of Period 3. Three patients were withdrawn because of adverse experiences, 1 of which was considered treatment related. Of 58 reports of adverse experiences, 8 were considered possibly related and 2 probably related to therapy. There was a total of 8 clinically significant abnormal laboratory values, 1 of which was considered to have a possible relation to therapy.

Cations in essential hypertension.

Sodium intake has been linked to the development and perpetuation of hypertension for almost a century. Nevertheless, considerable controversy over this relationship remain. More recently, the other major body cations, potassium, calcium and magnesium, have also been implicated. The evidence relating dietary sodium, potassium, calcium and magnesium intake to hypertension is summarized, and the present evidence for dietary modification of cation intake in the treatment of mild essential hypertension is evaluated.

Granulocyte differentiation in the lymphoid organs of chick embryos after antigenic and mitogenic stimulation.

Sections of spleen, bursa of Fabricius or thymus glands from 17-day-old chick embryos stimulated with sheep red blood cells, phytohaemagglutinin (PHA-P), concanavalin A or lipopolysaccharide were stained by an "indirect" peroxidase technique that differentiates eosinophils from heterophils and cell counts were carried out. The tissues were also examined with the electron microscope. Whatever stimulus had been used, the light microscopical examination revealed that the predominant granulocytes belonged to the peroxidase-negative heterophil series, outnumbering the peroxidase-positive eosinophils. There were no significant changes in the number of cells between treatments and the saline-injected controls, except in the case of PHA-P stimulation, where a slight reduction in the number of heterophils and a concomitant increase in eosinophils was observed. This study has demonstrated that the heterophil is the main granulocyte present in the lymphoid organs during late embryonic life in the fowl. It challenges previously reported work that the predominant cells are eosinophils and monocytes.

Beyond blood pressure control. Effect of antihypertensive therapy on cardiovascular risk factors.

Mild hypertension accounts for approximately 60% of the mortality associated with high blood pressure. In addition to hypertension, other major cardiovascular risk factors include left ventricular hypertrophy (LVH), dyslipoproteinemia, and glucose intolerance. Thus, the effects of agents used to treat hypertension on these risk factors are of considerable importance. Large therapeutic intervention trials have shown that while adequate treatment of mild hypertension significantly and consistently reduces all-cause mortality as well as the risk of stroke and congestive heart failure, an anticipated reduction in coronary heart disease (CHD) has not been demonstrated. It is possible adverse metabolic side effects (hypercholesterolemia, hyperglycemia, hypokalemia) of widely used agents, such as diuretics and beta-blockers may be partially offsetting the beneficial effects of blood pressure reduction, with the net result being a failure of these agents to reduce the risk of CHD. Angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers do not produce these adverse metabolic derangements. The use of antihypertensive agents that have favorable or neutral metabolic effects should further reduce the risk of cardiovascular morbidity and mortality attributable to high blood pressure, including CHD.

Role of insulin and norepinephrine in the hypertension of obesity.

The present study compares plasma norepinephrine (PNE), renin activity (PRA), aldosterone (PA), and insulin (RIAI) levels between 13 normotensive and 42 hypertensive obese subjects during weight maintenance, and in 19 of the 42 obese hypertensive subjects, these variables were measured during 16 weeks on a very low calorie diet (VLCD). Mean values for baseline RIAI and PNE were elevated in the 55 obese subjects compared to nonobese controls. However, when the normotensive and hypertensive groups were compared, mean values for PNE, PRA, PA, and RIAI were not different. In the 19 obese hypertensive subjects studied on the VLCD, there were significant reductions from baseline in mean body weight, blood pressure, RIAI, and PNE, but not for PRA or PA. Two phases of blood pressure, RAIA, and PNE responses to weight loss were noted. In the early phase (days 1-7), blood pressure and RAIA decreased dramatically, whereas PNE, PRA, and PA increased. During the late phase (weeks 2-16), further significant decreases in blood pressure and weight were accompanied by reductions in PNE (604 +/- 50 to 403 +/- 43 pg/mL, P < .01) and in RIAI (13.9 +/- 1.7 to 10.3 +/- 1.6 microU/mL, P < .05). As levels of insulin and norepinephrine were similar in normotensive and hypertensive obese individuals during weight maintenance, they may not contribute to the hypertension associated with obesity. During weight loss, however, the temporal changes in blood pressure, insulin, and norepinephrine suggest their mediation of the hypotensive response.

Mechanisms of hypertension in obesity.

We conclude that the following may explain the rise in blood pressure with obesity and the subsequent fall in blood pressure (Fig. 2): (1) An increase in calories, protein, or carbohydrate leads to an increase in plasma catecholamines, sympathetic nervous system activity, and insulin secretion. (2) These factors, in turn, lead to increased renal sodium retention and stimulation of the renin-aldosterone system which, in turn, leads to: (3) An increased cardiac output with an inability to appropriately adjust the peripheral resistance to maintain normotension with resultant hypertension. Conversely, the fall in blood pressure with weight reduction can be explained by (Fig. 3): (1) A decrease in calorie, carbohydrate, or protein intake which leads to: (2) A decrease in circulating plasma catecholamines, sympathetic nervous system activity, and insulin secretion which results in: (3) A natriuresis and decrease in the renin-aldosterone system, which causes a decrease in circulating blood volume and in cardiac output. This, in turn, lowers blood pressure towards normal. The unanswered question still remains: why do some obese patients become hypertensive and others remain normotensive? Perhaps there are weight-sensitive individuals and weight-resistant individuals just as there appear to be salt-sensitive and salt-resistant hypertensive patients. Perhaps the answer is genetic. These questions also remain to be answered.

Use of saralasin to detect renovascular hypertension in childhood.

Current methods to evaluate renovascular hypertension in the pediatric population often requires a general anesthetic. Saralasin, an angiotensin II competitive inhibitor, is a safe, noninvasive technique which can be utilized at the bedside in a salt-depleted child off antihypertensive medication. Two illustrative cases are presented.

Postmarketing survey of the effects of an atenolol/chlorthalidone combination in the treatment of hypertension.

A large-scale postmarketing survey was conducted in the United States to evaluate the antihypertensive efficacy and safety of a combination of 50 mg of the long-acting cardioselective beta-blocker atenolol and 25 mg of the monosulfonamyl diuretic chlorthalidone. The program included 28,585 patients (of whom 26,892 provided sufficient information by questionnaire for an assessment of efficacy and race), and the participation of 7,009 primary-care physicians. After four weeks of treatment, patients had a mean reduction in systolic blood pressure of 21 mmHg and in diastolic blood pressure of 13 mmHg. The magnitude of these reductions did not differ appreciably with respect to age, sex, race, or previous therapy. Diastolic blood pressure was reduced by at least 11 mmHg in 55% of patients and systolic blood pressure was reduced by at least 16 mmHg in 59% of patients. Physicians' assessments indicated that 86% of patients achieved satisfactory control of blood pressure by the end of the study. The physicians' global assessment of the effectiveness of treatment indicated that the combination was better than previous therapy in 82% of patients; 91% of physicians planned to continue treatment with the fixed combination. There were no adverse experiences that had not been reported previously, and only dizziness exceeded an incidence of 1%. It was concluded that the fixed combination provides added blood pressure control and the convenience of a simplified once-daily regimen without added side effects, regardless of age, sex, race, or prior antihypertensive therapy.

Systolic blood pressure as an independent predictor of mortality in the Hypertension Detection and Follow-up Program.

The Hypertension Detection and Follow-up Program (HDFP) findings demonstrate the predictive value of baseline systolic blood pressure (SBP) and of pulse pressure (PB) in five-year mortality from all causes. Grouping participants into four SBP strata revealed an approximately two-fold increase in age-adjusted mortality rate from SBP stratum I to SBP stratum IV. This effect remained after the contributions of other risk factors were controlled by multivariate analysis. In contrast, baseline diastolic blood pressure (DBP) had little demonstrable effect on mortality in this particular population. The predictive power of pulse pressure was similar to that of SBP. The group mean SBP of every stratum fell progressively during the trial, the change being of greater magnitude in the stepped care (SC) group than in the referred care (RC) group. Also, the reduction in all-cause mortality associated with SC treatment was observed at all levels of baseline SBP. An analysis using life table regression with SBP as a time-dependent variable showed that the postrandomization reduction in SBP was a significant factor in reducing mortality. Similarly, reduced DBP was also contributory. Prospective studies are required to answer definitively the question of the efficacy of treatment of systolic hypertension. Nevertheless, the present analysis of the HDFP data, despite design limitations, supports the advisability of reducing elevated systolic blood pressure.

Cations and hypertension: sodium, potassium, calcium, and magnesium.

The association between sodium intake and hypertension has been studied for almost a century. More recently, it has been suggested that abnormalities in dietary intake of potassium, calcium, and magnesium may play a major role in the pathogenesis of hypertension. A critical analysis of selected data from animal and human studies is discussed.

Renal vein renin: value and limitations in the prediction of operative results.

Renal vein renin determinations, in contrast to isolated peripheral venous renin determinations, provide great help in the selection of patients who can benefit from an operation for renal hypertension. Patients with essential hypertension usually have renal vein renin ratios, larger/smaller, close to unity, but the available cumulative data show that, statistically, ratios as large as 2.0 may occur in this group (95 per cent confidence limits). In patients with unilateral stenosis of a main renal artery, large renal vein renin ratios (stenotic/normal) have been followed by operative success in more than 90 per cent of patients. However, many operative successes have also been achieved in patients without a large renal vein renin ratio. This may be explained by inaccurate renal vein catheterization, inactive renin secretion, nonsimultaneous sampling, assay variability, and problems related to bilateral or segmental lesions. Recent refinements in the interpretation of renal vein renin data (contralateral suppression, ipsilateral hypersecretion in absolute terms, and a combination analysis scoring system) appear to increase the accuracy of the test. Detailed anatomic information, provided by arteriography, is essential for proper interpretation of renal vein renin data.

Dietary restriction on serum thyroid hormone levels.

To determine the long term effects of a protein sparing fast on serum thyroid hormone levels, the authors studied 38 obese patients ingesting a diet of 320 kcal for up to 13 weeks. The high baseline serum triiodothyronine (T3) levels decreased significantly by the first week, further decreased by the third week, and this lower level persisted for the duration of the fast until realimentation. Serum free T3 index followed the same general pattern as did serum T3 levels. Serum reverse T3 increased significantly by the first week, but by week three, the reverse T3 level had begun to fall, although still significantly increased above baseline. By week seven, reverse T3 had decreased to almost baseline and remained not significantly changed from the baseline to 13 weeks. Serum thyroxine (T4) increased significantly by the first week in all patients, but by the third week had returned to baseline levels which persisted to 13 weeks. The free T4 index and free T4 concentrations showed the same increment at week one and then returned to baseline levels. There were no significant changes in serum thyroxine-binding globulin (TBG) or thyroid-stimulating hormone (TSH) concentrations. The changes in serum T3 and reverse T3 levels are attributable to alterations in peripheral 5'-monodeiodination of T4 and reverse T3 induced by the protein sparing fast.

The fine structure of granules in eosinophil leucocytes from aquatic and terrestrial birds.

The ultrastructure of eosinophil granules from various aquatic and terrestrial birds has been described. Granules of three basic types were found. The first had a crystalline internum and was found only in the order Anseriformes, which included the black-necked screamer, ducks, geese and swans. The crystals occurred in three morphological forms. The second and least common granule examined contained a non-crystalline internum which was either homogeneous or composed of microfilaments or microtubules. The largest and most common group of birds had a homogenous granule with no internum shown. Homogeneous granules occurred less frequently than did those with interna.