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Biomedical subjects

G S Thind

Publications and source records attributed to G S Thind.

At least 19 recordsLinked to original sources

Cadmium-induced arteriolar constriction in skeletal muscle microcirculation.

Cadmium, an environmental pollutant, is known to induce hypertension in animal models, in part via an increase in peripheral vascular resistance. Since prior studies have investigated the vascular effects of cadmium using large, nonresistance arteries, we directly assessed cadmium's action on resistance size arterioles in skeletal muscle using the intact rat cremaster muscle preparation. Cadmium evoked a concentration-dependent constriction of the large arterioles (120 to 50 microns in diameter) but elicited no change in the diameter of smaller arterioles (30 to 15 microns). Blockade of alpha-adrenergic receptors did not diminish the constrictor response of the larger arterioles to cadmium, but bathing the cremaster muscles with a solution containing low calcium attenuated the arteriolar constriction to cadmium. Calcium repletion caused the arterioles to constrict further. These observations provide the first direct evidence that cadmium constricts resistance arterioles in skeletal muscle. The cadmium constriction: (1) is selective for the large arterioles, (2) is not mediated by alpha-adrenergic receptors, and (3) is influenced by the extracellular level of calcium. We conclude that arteriolar constriction in skeletal muscle tissue may play a role in the hypertensive actions of cadmium.

Animals

Angiotensin converting enzyme inhibitors: comparative structure, pharmacokinetics, and pharmacodynamics.

Angiotensin converting enzyme (ACE) inhibitors are a novel class of antihypertensive and anticongestive heart failure agents with wide patient and physician acceptability. By blocking the formation of angiotensin II in blood and tissue, all ACE inhibitors significantly lower systemic vascular resistance, lower blood pressure, and improve cardiac function, while maintaining or enhancing perfusion of vital organs: kidneys, brain, and heart. Captopril is the first oral ACE inhibitor with an active sulfhydryl group. Enalapril and lisinopril are potent nonsulfhydryl inhibitors of ACE characterized by weak chelating properties. The side effects of skin rashes, pruritus, taste abnormalities, oral ulcers, pemphigus, and blood dyscrasias have been considered to be strongly characteristic of penicillaminelike drugs, including the sulfhydryl ACE inhibitors. The class effects of cough, angio-edema, hyperkalemia, nonoliguric functional renal insufficiency, and hypotension can occur with equal frequency with all ACE inhibitors. It is unclear whether the many yet investigational ACE inhibitors would have distinct advantages over captopril, enalapril, lisinopril, and enalaprilat. This paper reviews the comparative structure and clinical pharmacology of the three commercially available but chemically different oral ACE inhibitors.

Administration, Oral

Demography predicts blood pressure response to once-daily enalapril monotherapy of mild to moderate essential hypertensive patients.

Enalapril was given once daily in low dose (5 to 10 mg) and high dose (20 to 40 mg) in 25 (15 white and 10 black) mild-to-moderate essential hypertensive patients. The white patients had a significant (p less than 0.005) supine diastolic blood pressure (SDBP) lowering with all doses of enalapril (from 97.2 +/- 1.8 to 85 +/- 2.4 mm Hg lowest). The black patient's SDBP did not decrease significantly (100.8 +/- 2.4 to 96.2 +/- 3.7 mm Hg lowest) with enalapril but addition of hydrochlorothiazide achieved satisfactory SDBP control. It is concluded that hydrochlorothiazide should be added if greater than 10 mg/day of enalapril is needed in white patients and the initial therapy in black patients should be a combination of enalapril and hydrochlorothiazide.

Black People

The effects of continuous intravenous naloxone on epidural morphine analgesia.

Forty-five patients undergoing Caesarean section under epidural anesthesia with bupivacaine were randomly allocated to three groups. Group 1 received 4 mg of epidural morphine immediately postoperatively and 2 mg naloxone by intravenous infusion for 12 hours postoperatively; group 2 was treated as group 1 but without naloxone infusion; group 3 received 10 mg morphine intramuscularly and 20 ml epidural saline after delivery of the baby. Epidural morphine 4 mg produced better postoperative analgesia than 10 mg of morphine intramuscularly (p less than 0.001) and the intravenous infusion of naloxone did not ablate the analgesic effects of epidural morphine. The incidence of itching and vomiting was higher in the epidural opioid groups (p less than 0.05) and intravenous naloxone, although it reduced the severity of the itching, did not reduce its overall incidence. Respiratory depression was not detected in any of the three groups.

Adolescent

A parallel study of enalapril and captopril and 1 year of experience with enalapril treatment in moderate-to-severe essential hypertension.

Angiotensin converting enzyme (ACE) inhibitors, enalapril (5 to 20 mg twice daily) or captopril (25 to 100 mg thrice daily) and matching ACE inhibitor placebos were given to 32 moderate-to-severe essential hypertension patients who were already on 50 mg hydrochlorothiazide daily. Alpha-methyldopa (250 to 500 mg twice daily) was given to 16 patients following 6 weeks of ACE inhibitor therapy. Both enalapril and captopril significantly (p less than 0.05) lowered the supine and upright blood pressures (BPs) (acutely and long-term) without significant reflex heart rate changes. The BPs of enalapril patients were, however, significantly lower (supine diastolic p less than 0.03, supine systolic p less than 0.05, and upright diastolic p less than 0.04) than those of captopril patients when compared by repeated measures of analysis of variance. Eleven enalapril patients have been followed for 1 year with continued BP control. Skin rash occurred in one captopril patient and reversible renal insufficiency developed in two enalapril patients during the first 16 weeks. It is concluded that (although both ACE inhibitors lowered BP, enalapril was more effective than captopril and twice-daily enalapril was well tolerated during 52 weeks of treatment.

Blood Pressure

Renal insufficiency during angiotensin-converting enzyme inhibitor therapy in hypertensive patients with no renal artery stenosis.

Worldwide experience with captopril and enalapril showed that angiotensin-converting enzyme (ACE) inhibitor monotherapy in hypertensive patients rarely caused renal dysfunction. The ACE inhibitors in combination with potent vasodilating drugs and diuretics may produce sudden systemic normotension or hypotension that may impair glomerular filtration at reduced renal perfusion pressure. Reversible renal insufficiency developed during the 13th week of hydrochlorothiazide-enalapril-alpha methyldopa therapy in patient 1 and during the 6th week of hydrochlorothiazide-enalapril treatment in patient 2. Systemic hypotension in patient 1 and routine biochemical monitoring in patient 2 was the first clue of renal insufficiency. Renal angiography was normal in both patients. Renal insufficiency resolved after stopping all drugs temporarily and did not recur on other antihypertensive drug regimens. These data suggested the importance of systemic arterial blood pressure as the best clinical determinant of renal function in hypertensive patients receiving an ACE inhibitor in combination with other antihypertensive agents.

Acute Kidney Injury

Enhancement of renal venous renin ratios by intravenous hydralazine in renovascular hypertension.

Renal venous renin (RVR) studies were done in 34 patients with moderate-to-severe hypertension before (unstimulated) and after (15- and 30-minute samples) a 20-mg bolus of i.v. hydralazine. The unstimulated lateralizing ratio of angiographically abnormal kidney or ipsilateral (I) to contralateral (C) RVR of greater than or equal to 1.5 was found in 69%, and the unstimulated ratio of I-inferior vena cava (IVC) renin below renal veins (I-IVC)/IVC (index of reduced renal blood flow) of greater than or equal to 0.48 was present in 50% of 16 patients (10 unilateral and 6 bilateral renal artery stenosis). The I/C and I-IVC/IVC ratios were abnormal in 100% and 88%, respectively, in 1 or both of the posthydralazine sampling in these patients. Hydralazine increased the absolute RVR from the ischemic kidney more than the contralateral kidney and did not result in new false-negative or positive I/C ratios. It is concluded that hydralazine stimulation of RVR is a safe and reliable way to determine the functionally significant pressor kidney in renovascular hypertension.

Clinical Enzyme Tests

Supraglottic obstruction.

A case of supraglottic obstruction resulting from a penetrating temporal injury is described. Despite the innocuous entry wound extensive occult injury had occurred and was initially overlooked. Diagnostic, anatomical and therapeutic considerations are discussed.

Airway Obstruction

Single dose suxamethonium and muscle pain in pregnancy.

The frequency of muscle pain was studied in two groups of patients. One group consisted of 106 women undergoing Caesarean section; the other comprised 20 pre-menopausal women undergoing hysterectomy. Both groups received a single bolus injection of suxamethonium 100 mg to facilitate tracheal intubation. There was a statistically significant decrease in the frequency of muscle pain in the pregnant group (7.5%) compared with the non-pregnant group (30%).

Adult

Low-dose captopril titration in patients with moderate-to-severe hypertension treated with diuretics.

To study the value of low-dose captopril (6.25 and 12.5 mg) and a diuretic combination, the blood pressure and heart rate of 17 patients with moderate-to-severe hypertension were monitored for 6 hours (hospital) or 3 hours (office) after the single low-dose or larger (25, 50, 100 and 150 mg) captopril dosage. All patients had preserved renal function and were taking an oral diuretic (hydrochlorothiazide or furosemide) for at least 4 weeks. The supine and upright acute blood pressure lowering with 6.25 mg was not different from the larger captopril doses; none produced persistent or profound hypotension. There was no deterioration of renal function, new or persistent increase in proteinuria, neutropenia or agranulocytosis acutely or during 17 +/- 2 weeks of follow-up. Low-dose captopril (6.25 or 12.5 mg three times daily) normalized the supine blood pressure of 35% of these patients acutely. We suggest that in hypertensive patients already taking a diuretic, a lower starting dose of captopril than the recommended 25 mg three times daily may be desirable.

Adult

Newer antihypertensive agents.

There are very few areas of clinical pharmacology being pursued as vigorously as hypertension. Numerous new drugs are being discovered and tested both in United States and overseas. The most promising new antihypertensive drugs seem to fall into the angiotensin-renin blocker group and those affecting the sodium-volume axis in hypertensive patients. We can look forward to newer agents that are efficacious as monotherapy and on a daily or twice daily dosage regimen for the treatment of the vast majority of hypertensive patients. There is further hope that preoperative evaluation with angiotensin blockers in patients with renovascular hypertension may improve the predictability of successful renal bypass surgery.

Aged

The biology of cadmium.

Industrial exposure to large amounts of cadmium is known to be toxic to man; however, the low levels of cadmium in water, food, and air to which everyone is continually exposed have no obvious effects. During childhood and adolescence, ingestion and inhalation of cadmium are responsible for the average American accumulating about 30 mg of cadmium in his body, with the highest concentration being in the kidney. It has been suggested on the basis of two observations that elevated renal cadmium might be associated with essential hypertension: (1) Hypertensives have been reported to have higher renal cadmium concentrations than normotensives. (2) Long-term exposure to low levels of cadmium has reproducibly caused mild hypertension in animals. Finally, increased levels of cadmium have been found in lungs and other tissues of emphysematous subjects.

Adolescent

Plasma cadmium and zinc in human hypertension.

1. Plasma cadmium and zinc were determined by atomic absorption spectrophotometry in inferior venal caval or peripheral venous blood in thrity hypertensive patients and fifteen normal subjects. 2. The mean plasma cadium in hypertensive patients was significantly higher than in normal control subjects. 3. The plasma cadmium/zinc ratio was significantly greater in hypertensive patients. 4. There was a significant positive correlation between the plasma cadmium/zinc ratio and the mean arterial blood pressure.

Adult