Search PubMed⌕ Search

Biomedical subjects

S L Swartz

Publications and source records attributed to S L Swartz.

36 records · Page 2Linked to original sources
PubMed1983

Response of the kidney to furosemide. II. Effect of captopril on sodium balance.

We investigated the role of the renin-angiotensin-aldosterone (RAA) system during furosemide (F) administration. The effects of adding captopril (C) (25 mg . 6 hr-1) to F (40 mg daily for 3 days) were studied in six normal subjects equilibrated to a daily sodium (Na) intake of 270 mmoles. Without C, F produced a marked natriuresis but Na+ excretion fell sharply between drug doses. This resulted in neutral Na balance (+22 +/- 58 mmoles . 3 days-1; mean +/- SE). Plasma angiotensin (AII) and aldosterone (Aldo) rose, but mean blood pressure (MBP) was unaltered. C abolished the F-induced increases in AII and Aldo but did not modify the pattern of Na+ excretion. Na+ balance remained neutral (+42 +/- 54 mmoles . 3 days-1). With C alone, Na+ balance was positive (+110 +/- 30 mmoles . 3 days-1; P less than 0.02). In protocols C alone and F + C, MBP fell by a comparable amount. F alone and F + C increased plasma norepinephrine and prostaglandin E2 metabolite; these did not change with C alone. In conclusion, activation of the RAA system by F is not essential for the compensatory increase in Na+ reabsorption that maintains Na+ balance after F.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1983

Role of prostaglandins in adrenal steroidogenesis.

Using an in vitro rat glomerulosa and fasciculata cell preparation, we studied the role of porstaglandins (PGs) as potential mediators of angiotensin II-, ACTH-, and potassium-induced adrenal steroidogenesis. The glomerulosa cells primarily produced prostacyclin under basal and stimulated conditions, whereas the fasciculata cells primarily produce PGF2 alpha. Using 6-keto-PGF1 alpha (the stable hydrolysis product of prostacyclin) and PGF2 alpha as indices of PG production in glomerulosa and fasciculata cells, respectively, we noted no significant changes in PGs during angiotensin II-, ACTH-, or potassium-induced steroidogenesis. Pretreatment with indomethacin significantly (P less than 0.01) inhibited PG production, but did not alter adrenal steroidogenesis. Furthermore, the administration of exogenous PGs did not affect steroidogenesis. We conclude that PGs do not mediate steroidogenesis from rat glomerulosa or fasciculata cells.

6-Ketoprostaglandin F1 alpha↗
PubMed1982

Angiotensin-converting enzyme inhibition and prostaglandins.

To determine whether prostaglandins contribute to the depressor response of angiotensin-converting enzyme inhibitors, plasma prostaglandin levels were measured by radioimmunoassay in normo- and hypertensive subjects on both sodium-restricted and sodium-loaded diets before and after captopril administration. On the sodium-restricted diet, the hypotensive response to captopril was accompanied by significant increments in the metabolite of prostaglandin E2 (PGE2-M) and bradykinin and by significant decrements in angiotensin II. The high sodium diet suppressed the response of the renin-angiotensin and kinin systems to captopril but the hypotensive response persisted. Furthermore, the decrease in blood pressure correlated significantly with increments in prostaglandin E2-metabolite. Prostaglandin synthesis was then inhibited in the sodium-restricted hypertensive patients by pretreatment with indomethacin. This maneuver completely eliminated the captopril-induced prostaglandin E2-metabolite increment without changing bradykinin or angiotensin II responses but significantly attenuating the hypotensive response. Finally, when patients were studied on a high sodium intake, similar effects were observed except now indomethacin completely abolished the blood pressure response to captopril. These studies therefore support the hypothesis that increased production of vasodilator prostaglandins in a major mediator of the hypotensive response to captopril. Whether the change in prostaglandin release is a direct effect of the drug or secondary to increased kinin levels is uncertain.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Partial peripheral resistance to thyroid hormone.

A 33 year old partially thyroidectomized woman was euthyroid when ingesting 500 microgram of L-triiodothyronine (T3) daily. Her condition was evaluated during therapy with daily T3 doses between 50 and 500 microgram. She was hypothyroid and had a markedly subnormal oxygen consumption rate when taking 50 to 100 microgram T3 daily, and oxygen consumption did not increase greatly above predicted normal values despite serum T3 concentrations up to 3,200 ng/dl. Her pulse rate, blood pressure, systolic time intervals and exercise tolerance changed minimally and remained within the normal range during the different dosage schedules. Urinary creatine and hydroxyproline, indices of muscle and skeletal protein catabolism, increased normally with higher T3 doses, but serum cholesterol, creatine phosphokinase, calcium and alkaline phosphatase did not change substantially. Basal and thyrotropin-releasing hormone (TRH) stimulated thyrotropin secretion were suppressed during all T3 doses. The prolactin response to TRH was normal at 50 microgram T3/day and was reduced by higher doses of T3. Absorption of T3, serum T3 protein binding and T3 metabolic clearance rates were all within normal limits. The findings in this patient are compared to clinical and biochemical findings in 17 previously described patients. The manifestations of peripheral thyroid hormone resistance are quite variable in the organ systems involved and in the degree of involvement. The molecular basis of the abnormality in our patient remains undefined.

Adolescent↗
PubMed1980

Increase in prostaglandins during converting enzyme inhibition.

1. Because changes in the plasma concentration of angiotensin II and bradykinin appear inadequate to account completely for the hypotensive response to captopril, we measured changes in plasma prostaglandins in response to increasing doses of captopril in nine supine normal male subjects studied on both a high (200 mol/l) and low (10 mol/l) sodium intake. 2. On both the high and low sodium diets, captopril induced significant (P < 0.01) increments in the 13,14-dihydro-15-keto metabolite of the vasodilatory prostaglandin E2, which correlated significantly with the fall in blood pressure (P < 0.0001). 3. No significant changes were noted in the plasma levels of 6-keto-prostaglandins F1 alpha or thromboxane B2, the stable products of prostacyclin and thromboxane A2 respectively.

Adult↗
PubMed1980

Captopril-induced changes in prostaglandin production: relationship to vascular responses in normal man.

Captopril is a potent hypotensive agent whose efficacy has hitherto been attributed to its ability to alter either angiotensin II formation or kinin degradation. Our purpose was to examine captopril's acute effect on prostaglandin production, because changes in neither the renin-angiotensin nor the kallikrein-kinin systems appear adequate to account for the fall in arterial pressure. The plasma levels of angiotensin II, kinins, and prostaglandins were determined in response to increasing doses (5, 12.5, and 25 mg) of captopril and these responses were compared with the change in arterial pressure observed in nine supine normal male subjects studied on both a high (200 meq) and low (10 meq) sodium intake.Captopril significantly (P < 0.01) increased the levels of the 13,14-dihydro-15-keto metabolite of prostaglandin E(2) (PGE(2)-M), a potent vasodilator, with similar responses being observed on both a high and a low sodium intake. No significant changes in the plasma levels of 6-keto-prostaglandin F (1)alpha, or thromboxane B(2), the stable products of prostacyclin and thromboxane A(2), respectively, occurred. The depressor response to captopril correlated with the change in PGE(2)-M (r = 0.52, t = 5.44, P < 0.0001). On the other hand, although significant (P < 0.02) decrements in angiotensin II and increments in plasma kinins accompanied the hypotensive response in sodium-restricted subjects, in sodium-loaded subjects where the renin-angiotensin system was suppressed, no change in angiotensin II, and only a modest change in kinins was noted, even though significant (P < 0.01) decrements in diastolic blood pressure occurred (-10+/-2 mm Hg).Thus, changes in depressor prostaglandin production can better account for the hypotensive response to captopril, thereby extending to yet another vasoactive system an influence by this class of drugs and providing a new approach to dissecting the abnormality in the control of vascular tone in patients with hypertension.

Adult↗
PubMed1980

Primacy of the renin-angiotensin system in mediating the aldosterone response to sodium restriction.

The primacy of angiotensin II as the mediator of the adrenal's response to sodium restriction is controversial. We administered the oral converting enzyme inhibitor, captopril (SQ 14225), to test whether reduction of angiotension II generation for 26 h in sodium-restricted subjects would lower plasma aldosterone levels to values observed in subjects on a high sodium intake. Accordingly, plasma angiotensin II and aldosterone levels were measured in nine recumbent normal subjects on high (200 meq) and low (10 meq) sodium intakes and low sodium intake with captopril (12.5--25 mg four times a day for 26 h). Captopril reduced the sodium-restricted angiotensin II levels from 31 +/- 6 to 13 +/- 2 pg/ml, which was indistinguishable from that measured on the high sodium intake (11 +/- 2 pg/ml). Concomitantly, aldosterone levels were reduced from 25 +/- 4 to 7 +/- 1 ng/dl, which was similar to the high sodium value (8 +/- 1 ng/dl). There were no significant changes in serum sodium, cortisol, or potassium at the three sampling times. Thus, the complete suppression of the sodium-restricted levels of both angiotensin II and aldosterone into the high sodium range by captopril provides strong support for the hypothesis that the renin-angiotensin system is the prime mediator of the adrenal's response to sodium restriction.

Adult↗
PubMed1979

Increased glomerular filtration rate after converting-enzyme inhibition in essential hypertension.

To test the influence of an inhibitor of angiotensin-converting enzyme, teprotide (SQ 20881), we administered it to seven patients with essential hypertension and normal renal function and nine with an unequivocal reduction in creatinine clearance, caused by bilateral renal-artery stenosis in two and by essential hypertension in seven. Despite the fall in blood pressure (112.7 +/- 4.5 to 100.3 +/- 3.9 mm Hg, mean +/- S.E.M., P less than 0.01), there were prompt increases in both creatinine clearance (95.9 +/- 10.5 to 109.9 +/- 9.5 ml per minute per 1.73 m2 of body-surface area, P less than 0.01) and sodium excretion (17.0 +/- 5.9 to 31.7 +/- 7.2 mumol per minute, P less than 0.01) in patients with essential hypertension. The increase in glomerular filtration rate was most striking, averaging 33 per cent (66.0 +/- 10.3 to 88.0 +/- 9.2 ml per minute per 1.73 m2, P less than 0.001) in patients in whom an initial reduction was evident and hypertension was more severe. These observations suggest that a functional element, perhaps involving angiotensin-mediated renal vasoconstriction, frequently has a role in the reduction in glomerular filtration rate that occurs in essential hypertension. This class of agent may improve renal excretory function as it controls hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1979

Persistent urethral leukocytosis and asymptomatic chlamydial urethritis.

Chlamydia trachomatis was isolated from 47% of asymptomatic, sexually active men whose urethral smears contained four or more polymorphonuclear leukocytes (PMN) per high-power field (hpf) one week after their sexual activity was restricted. C. trachomatis was not detected in any of 23 asymptomatic, sexually active men having less than 4 PMN/hpf in two urethral smears obtained one week apart. Semiquantitation of urethral PMN in the urethral Gram-stained smear is useful in the evaluation of asymptomatic men without gonorrhea who are concerned about the possibility of harboring a urethral pathogen.

Chlamydia Infections↗
PubMed1979

The adrenal receptor for angiotensin II is altered in essential hypertension.

To determine the mechanism underlying altered adrenal responsiveness in patients with essential hypertension, the renin-angiotensin-aldosterone axis was assessed in normotensive and hypertensive subjects using three pharmacological probes: SQ 20881, a converting enzyme inhibitor; saralasin, a competitive angiotensin antagonist with prominent agonist properties; and angiotensin itself. All subjects were studied while supine and in balance on a 10 meq Na/100 meq K intake. The decrement in plasma aldosterone with SQ 20881 in 26 hypertensive subjects (15+/-3 ng/dl) was normal (13+/-4 ng/dl), suggesting that the altered adrenal responsiveness in hypertensives is not because of a change in a postreceptor event or in the relative contribution of angiotensin to the control of aldosterone secretion. Saralasin at a dose (0.1 mug/kg per min) that reduced aldosterone levels in all normals produced a normal aldosterone decrement (14+/-3 ng/dl) in 19 patients with renovascular hypertension (12+/-4 ng/dl). The same dose, however, had no net effect on plasma aldosterone levels in 70 patients with normal or high renin essential hypertension (-1+/-1 ng/dl) despite identical metabolic balance and control renin and angiotensin levels. The altered response could be explained by an agonist effect, aldosterone rising in 45 of the essential hypertensives. There were no significant differences between normal and abnormal responders in pre- and postcortisol, -potassium, -renin and -angiotensin concentrations. Angiotensin was infused (0.1-3 ng/kg per min) in 15 patients with normal renin essential hypertension, previously studied with saralasin. A probit transformation defined the dose required to induce a 50% increase in aldosterone (ED50). In the patients in whom aldosterone rose with saralasin, the dose required to induce a 50% increase was significantly greater (P < 0.001) than in those in whom aldosterone fell normally (1.02+/-0.06 [SD] vs. 0.38+/-0.07 ng/kg per min). Vascular responses were similar in the various groups. We conclude that altered adrenal responsiveness to angiotensin in some essential hypertensive patients is secondary to a change in the interaction of angiotensin with its adrenal receptor.

Adrenal Glands↗
PubMed1978

Diagnosis and etiology of nongonococcal urethritis.

The observation of more than four polymorphonuclear cells (PMN) per high-power field (hpf) in gram-stained smears of urethral secretions was found to differentiate patients with urethritis from patients without urethritis. A urethral discharge was present in 78% of patients with nongonococcal urethritis (NGU). Dysuria without demonstrable urethral discharge and with fewer than four PMN/hpf did not appear to fit into the NGU spectrum. NGU is now defined to include men who have negative urethral cultures for Neisseria gonorrhoeae with a urethral discharge and/or more than four PMN/hpf in their urethral smears. The findings of more than four PMN/hpf in the urethral smears of 22%of asymptomatic sexually active men with more than one sexual partner (polygamous controls) suggests that asymptomatic NGU is not uncommon. Chlamydia trachomatis was isolated significantly more frequently from the NGU study group than from the control group (P less than 0.001). This study adds Corynebacterium vaginale (Haemophilus vaginalis), group B streptococci, and yeasts to the list of sexually transmitted microorganisms that are not etiologic determinants of NGU.

Chlamydia trachomatis↗
PubMed1978

Corticosteroids: clinical pharmacology and therapeutic use.

The widespread use of corticosteroids in clinical practice emphasises the need for a thorough understanding of their metabolic effects. In general, the actions of corticosteroids on carbohydrate, protein, and lipid metabolism result in increased hepatic capacity for gluconeogenesis and enhanced catabolic actions upon muscle, skin, lymphoid, adipose and connective tissues. Because of the morbidity associated with steroid therapy, the clinician must carefully consider in each case the gains that can reasonably be expected from corticosteroid therapy versus the inevitable undesirable side effects of prolonged therapy. Thus, it is important to remember that the enhanced anti-inflammatory activity of the various synthetic analogues of cortisol is not dissociated from the expected catabolic actions of glucocorticoid hormones. Replacement therapy with physiological doses of cortisol in primary or secondary adrenal insufficiency is intended to simulate the normal daily secretion of cortisol. Short term, high dose suppressive glucocorticoid therapy is indicated in the treatment of medical emergencies such as necrotising vasculitis, status asthmaticus and anaphylactic shock. With improvement of the underlying disorder, the steroid dosage can be rapidly tapered and then discontinued over a 2 to 3 day period. Long term, high dose suppressive therapy is often commonly used to treat certain diseases (see sections 4.7.2 and 4.7.3). In this setting, suppression of the hypothalamic-pituitary-adrenal axis may persist for as long as 9 to 12 months following steroid withdrawal if steroid doses are administered in the supraphysiological range for longer than 2 weeks. In general, higher doses, longer duration of usage, and frequent daily administration are all correlated with the severity of pituitary ACTH suppression. When steroid therapy is to be withdrawn, gradual tapering of the dosage is necessary; the steroid dosage should also be given as a single morning dose if possible. Rapid or total withdrawal of the steroid therapy may be associated with exacerbation of the underlying disease or with a steroid withdrawal syndrome. An additional important point to remember in any withdrawal programme is that the steroid dosage should be appropriately increased for an exacerbation of the underlying disease or for intercurrent major stress. Alternate day therapy is recommended as a steroid maintenance programme for patients requiring high dose glucocorticoid therapy over a prolonged period of time. Thus, it is usually employed to maintain a therapeutic benefit which had previously been extablished by daily steroid treatment. Complications resulting from corticosteroid therapy include: (1) proximal muscle weakness; (2) osteopenia; (3) unmasking of latent diabetes mellitus; (4) sodium retention and/or elevation of mean arterial blood pressure; (5) adverse psychiatric reactions; (6) development of glaucoma; and (7) reactivation of latent infections (such as tuberculosis).

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Time course and effect of sodium intake on vascular and hormonal responses to enalapril (MK 421) in normal subjects.

Enalapril (MK 421) is a long-acting angiotensin converting-enzyme inhibitor which specifically lacks the sulfhydryl group of captopril. We measured arterial pressure and hormonal responses that occurred in 22 normotensive subjects treated with increasing doses of enalapril (2.5, 5, 10, and 20 mg) once daily, who were on either low (10 mEq) or high (200 mEq) sodium diets. In sodium-restricted subjects (n = 12), mean diastolic blood pressure declined from control levels in a dose-related fashion during the first 2 h. The mean 24-h diastolic blood pressure values were significantly lower than control (p less than 0.01) at all doses, with the greatest declines occurring with the 10 and 20 mg doses. Accompanying the decline in blood pressure was a significant increase in plasma renin activity (PRA) and reduction in plasma angiotensin II (AII) and aldosterone levels. As with blood pressure, the greatest changes were observed with the 5, 10, and 20 mg doses. However, only the 20 mg dose of enalapril produced prolonged and significant PRA increments (p less than 0.01) and AII decrements (p less than 0.05) of at least 24 h in duration. In sodium-replete subjects (n = 10), a similar pattern of diastolic blood pressure responses was observed; however, the effect of the drug was not so profound. No significant decrease in AII occurred at any dose of enalapril; however, PRA increased modestly but significantly (p less than 0.01) after administration of 5, 10, and 20 mg enalapril. Plasma aldosterone declined modestly but significantly, 2 (p less than 0.05) and 4 (p less than 0.01) h after the 10 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation.

To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition.

Adolescent↗
PubMedDate not supplied

Differences in response to the peptidyldipeptide hydrolase inhibitors SQ 20,881 and SQ 14,225 in normal-renin essential hypertension.

We compared vascular and hormonal responses to teprotide (SQ 20,881) and captopril (SQ 14,225) in patients with normal renin essential hypertension given a 10 mEq sodium diet. In 10 patients receiving SQ 20,881, significant changes occurred in diastolic blood pressure (DBP, -13 +/- 2.5 mm Hg), angiotensin II (-7.1 +/- 2.1 pg/ml), and plasma renin activity (PRA, +6.6 +/- 1.9 ng/ml/hr) (p < 0.01 in all cases). Twenty-one patients receiving SQ 14,225 had significant changes in mean DBP (-18 +/- 1.5 mm Hg), angiotensin II (-6.6 +/- 1.5 pg/ml), and PRA (+7.8 +/- 2.4 ng/ml/hr) (all p values < 0.01). In spite of a significantly greater hypotensive response (p < 0.02), patients receiving SQ 14,225 showed increments in PRA and decrements in angiotensin II that did not differ significantly from those seen after SQ 20,881. Moreover, there was a significant change in plasma kinins in patients receiving SQ 20,881 (+2.0 +/- 0.9 ng/ml, p < 0.01) but no change in kinins in patients receiving SQ 14,225 (0.0 +/- 0.1, ns). We conclude that there are important differences in the mechanism mediating the hypotensive response to SQ 20,881 and SQ 14,225 in normal renin essential hypertension.

Adult↗
PubMedDate not supplied

Contribution of prostaglandins to the antihypertensive action of captopril in essential hypertension.

To determine whether prostaglandins contribute to the depressor response to the converting enzyme inhibitor, captopril, we measured the plasma prostaglandin levels by radioimmunoassy before and after captopril administration, and then examined the effect of prostaglandin synthetase inhibition on captopril's antihypertensive effect. When a single oral captopril dose (25-100 mg) was given to 31 sodium-restricted patients with essential hypertension, the levels of the stable transformation product of prostacyclin remained unmeasurable and that of thromboxane A2 did not change, while the metabolite of PGE2 (PGE-M) increased by 53% (34 +/- 4pg/ml pre-captopril, 52 +/- 5 pg/ml after; p less than 0.001). As expected, blood pressure (BP) and angiotension II (AII levels fell, and kinin levels rose (all changes p less than 0.001). We then blocked prostaglandin synthesis in 18 of these subjects for 24 hours with either indomethacin (n = 10) or aspirin (n = 8) before repeating the captopril dose, to assess the importance of these PGE-M increments. The PGE-M responses to captopril were effectively blocked in nine of 10 subjects receiving indomethacin and four of eight receiving aspirin. In these 13 patients, the depressor response to captopril was significantly blunted (-20 +/- 3mm Hg pre-synthetase inhibition vs - 13 +/- 2 mm Hg post; p less than 0.05). When these agents did not block the PGE-M response to captopril, the BP response was also unchanged (-15 +/- 4mm Hg pre, -18 +/- 5mm Hg post). Neither indomethacin nor aspirin changed the AII or kinin responses to captopril. We conclude that the prostaglandins may be important mediators of captopril's antihypertensive effect in the sodium-restricted state.

Adult↗
PubMedDate not supplied

Biochemical markers of compliance in the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer. To evaluate self-reported compliance with assigned treatment, we measured serum thromboxane B2, which is decreased after aspirin use, and plasma beta-carotene in samples of study participants drawn from three geographic locations in three different time periods. Thromboxane B2 levels were markedly lower in those assigned to aspirin (median = 63.5 pg/mL) than in those given aspirin placebo (median = 3,600 pg/mL, P less than .0001). Similarly, those assigned to beta-carotene had significantly higher levels (median = 1,176 ng/mL) than those given placebo (median = 306 ng/mL, P less than .0001). In addition, there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance (r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene, P less than .0001). These findings support the validity of the self-reported compliance in the Physicians' Health Study.

Adult↗