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Biomedical subjects

J G Porush

Publications and source records attributed to J G Porush.

At least 37 records · Page 2Linked to original sources

Reversal of Na+ retention in chronic caval dogs by verapamil: contribution of medullary circulation.

The effects of verapamil on papillary plasma flow (PPF) and Na+ excretion were studied in anesthetized chronic caval dogs with low cardiac output and Na+ retention. Infusion of verapamil into the left renal artery (5 and 10 micrograms.kg-1.min-1) caused a dose-dependent ipsilateral increase in renal blood flow and Na+ excretion (from 10 +/- 2 to 171 +/- 32 and 225 +/- 35 mu eq/min, respectively). PPF in the left kidney was 26.6 +/- 4.4 and was significantly greater than that measured in the contralateral kidney (13.3 +/- 2.4 ml.min-1.100 g-1) (P < 0.01). The natriuresis occurred independent of changes in cardiac output and peripheral vascular resistance. In a separate group of caval dogs in which stimulation of the renin-angiotensin and adrenergic systems was intensified with a tighter caval constriction, verapamil failed to induce renal vasodilation or natriuresis and PPF was not altered. Despite the disparate hemodynamic responses, verapamil stimulated renal production of both renin and prostaglandin E2 in both groups of caval dogs. We conclude that the ability of verapamil to induce papillary vasodilation may contribute to the natriuresis seen in the caval dog, in which the site of Na+ retention includes the loop of Henle.

Animals↗

Hypertension and renal insufficiency: recognition and management.

The incidence of end-stage renal disease among hypertensive patients is increasing. Early recognition of renal insufficiency is critically important, since reversible causes of renal failure, such as urinary tract obstruction and renal artery stenosis, may be identified and corrected. Control of hypertension slows the progression of renal failure. Once renal failure develops, special attention must be given to diet and drug therapy.

Humans↗

Effective hypertension control in inner city blacks.

A clinic for patients with "resistant" hypertension was established and patients were followed by one physician, nurse, and secretary. The records of 105 randomly chosen patients out of 700 were reviewed. In 86 of 105 (82%), diastolic blood pressure was controlled (less than 90 mm Hg) (group I), but in 19 patients, after 54 +/- 6 (mean +/- standard error) months, it remained greater than 90 mm Hg (group II) with substantial improvement in 53% (10 of 19 patients). The two groups were similar in age (57 +/- 1 vs 54 +/- 3 years), race (84% vs 74% blacks), and sex (75% vs 86% female). The entry blood pressures in groups I and II were similar, 170 +/- 3/101 +/- 1 and 167 +/- 6/105 +/- 3 mm Hg, respectively. Last visit blood pressure was 130 +/- 1/79 +/- 1 in group I, lower than 156 +/- 5/94 +/- 2 in group II (p less than 0.05). At entry into the clinic and at the last visit, dosing and type of medications were similar in both groups. Although patient visits averaged 6.7/yr in both groups, patients in group II missed 1.7 +/- 0.3 compared with 0.9 +/- 0.1 visits/year for group I (p less than 0.01). Group II patients were also less compliant with medications, primarily because of psychosocial problems. Medications, however, were more available to this group, since 16 of 19 (84%) were Medicaid recipients, compared with 46 of 86 (53%) in group I (p less than 0.025).(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive Agents↗

The incidence and epidemiology of human immunodeficiency virus infection in 320 patients treated in an inner-city hemodialysis center.

From January 1, 1986 through June 30, 1989, 320 maintenance hemodialysis patients treated at The Brookdale Hospital Medical Center were tested for the presence of antibody to the human immunodeficiency virus (HIV) using the enzyme-linked immunosorbent assay (ELISA) and Western blot assays. Thirty-nine patients (12%) tested positive for HIV antibody (HIV+) with both the ELISA and Western blot, 24 (62%) of whom were known intravenous drug abusers (IVDA). Of the remaining non-IVDA patients, unanticipated HIV+ results were found in 10 (25%). Thirty-four (87%) of the 39 HIV+ patients were asymptomatic at the start of the study, while two had acquired immunodeficiency syndrome (AIDS) and three others, AIDS-related complex (ARC). Four patients subsequently developed AIDS 20 +/- 4.9 weeks (range, 12 to 32) after testing, three of whom initially had ARC. One patient developed ARC 7 months after testing. Sixteen HIV+ patients died, including five of the six with AIDS, one with ARC, and two others from Mycobacterium tuberculosis. The eight other deaths were from causes unrelated to HIV disease and occurred 12 +/- 2.3 months (range, 1 to 24) after testing. Two HIV+ patients were lost to follow-up. Twenty-one HIV+ patients (54%) are alive and 20 (51%) asymptomatic 15 +/- 2.4 months (range, 1 to 42) after HIV testing. Thus, despite HIV positivity, 28 patients (72%) had an asymptomatic period lasting 14 +/- 1.9 months (range, 1 to 42). Seventy-two of the 281 HIV-negative (HIV-) patients died during the study. None of the HIV- patients manifested ARC or AIDS, confirming that there was no false-negative HIV test.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Serodiagnosis↗

Renal medullary circulation: hormonal control.

It is now becoming apparent that the medullary circulation in the kidney can be regulated separately from overall renal blood flow. This characteristic of the medullary circulation plays an important role in the kidney's ability to excrete a dilute or concentrated urine in concert with changes in water and sodium transport in the distal nephron secondary to the action of vasopressin, prostaglandins, the renal nerves, and other hormones without significant other renal hemodynamic changes. There is strong evidence that renal autocoids such as angiotensin II and prostaglandins uniquely affect regional blood flow in the inner medulla because of the special structure and organization of the microvasculature in this region. There is also evidence that this regional blood flow is in part regulated by circulating hormones, such as vasopressin and atrial natriuretic peptide, which are released in response to changes in extracellular fluid volume or osmolality. In addition, data are emerging to suggest that the kallikrein-kinin system, acetylcholine, the renal nerves and adenosine participate in this regulation. In addition to the role of the medullary circulation in the urinary concentrating operation, there are data to suggest that the medullary circulation either directly (by changes in physical forces) or indirectly (by regulating medullary toxicity) may influence sodium excretion in a variety of conditions. In this regard, activation of the renin-angiotensin system locally reduces blood flow in the papilla which may be necessary before sodium retention is fully expressed in salt retaining states. Future research looking at the microvasculature of the medulla and papilla and those factors that control the contractility of these vessels are necessary before a clearer picture emerges. Nevertheless, from the data already available it seems reasonable to suggest that the medullary circulation may be as important to kidney function during physiological and pathophysiological states as is the cortical circulation.

Acetylcholine↗

Renal actions of endothelin: interaction with prostacyclin.

The renal actions of endothelin were examined by infusing it intrarenally in anesthetized dogs at 4 ng.min-1.kg-1 without affecting arterial blood pressure or cardiac output. Endothelin infusion caused a transient and significant increase in renal blood flow (RBF) by 13 +/- 2%, followed by large decreases in RBF and glomerular filtration rate (GFR; by 26 +/- 2 and 23 +/- 7%, respectively) but did not alter urine flow rate or absolute sodium excretion. After endothelin infusion, renal venous and arterial plasma 6-ketoprostaglandin F1 alpha increased from 250 +/- 58 and 117 +/- 31 to 1,044 +/- 249 and 617 +/- 211 pg/ml, respectively, and its renal output increased from 339 +/- 99 to 963 +/- 202 pg.min-1.g-1 (P less than 0.01 for all). The renal prostacyclin synthesis was augmented by endothelin without stimulating the renal renin release or norepinephrine output. Inhibition of prostaglandin synthesis with indomethacin partially prevented the early renal vasodilation induced by endothelin, which then caused a more pronounced decline in RBF and GFR (by 65 +/- 7 and 54 +/- 8%, respectively). With suppression of prostacyclin synthesis, inhibition of renin release by endothelin was observed. Thus the vasoconstrictive effects of endothelin on renal hemodynamics are significantly modified by its ability to enhance production of vasodilators, including prostacyclin.

6-Ketoprostaglandin F1 alpha↗

Comparison of nifedipine and propranolol used in combination with diuretics for the treatment of hypertension.

One hundred patients participated in a double-blind, randomized study to compare the antihypertensive efficacy of sustained-release nifedipine and propranolol in hypertensive patients whose diastolic blood pressure exceeded 95 mm Hg while receiving diuretic therapy. Nifedipine (mean dose, 79.6 mg per day) decreased blood pressure by 11.4/10.5 mm Hg; propranolol (mean dose, 198.4 mg per day) decreased blood pressure by 13.5/10.3 mm Hg. Reduction of diastolic blood pressure to below 90 mm Hg was achieved in 63 percent of nifedipine-treated patients and in 57 percent of propranolol-treated patients. Nifedipine therapy was associated with an increase in high-density lipoprotein cholesterol levels and a decrease in serum triglyceride levels. In contrast, propranolol therapy was associated with a decrease in high-density lipoprotein cholesterol levels and an increase in serum triglyceride levels. Nifedipine is as effective as propranolol in the treatment of patients with mild to moderate hypertension whose blood pressure is inadequately controlled by diuretic therapy.

Adult↗

Regulation of papillary plasma flow by angiotensin II.

We examined in anesthetized dogs the effects of left (L) intrarenal artery infusion of angiotensin II (AII) on renal hemodynamics, urinary concentration and Na excretion, and papillary plasma flow (PPF) (measured by the albumin accumulation technique) in both kidneys. Following AII infusion (0.5 ng/kg/min) into the L renal artery, urinary Na excretion decreased and osmolality increased slightly ipsilaterally, whereas Na excretion did not change significantly and osmolality decreased in the right (R) kidney. PPF was significantly lower in the L compared to the R kidney. When saline loading was superimposed on L intrarenal AII infusion, there was a blunted natriuretic response ipsilaterally with a significantly smaller decrease in urine osmolality compared with the R kidney. PPF increased significantly in the R, but not in the L kidney. Finally, AII blockade with saralasin prior to AII infusion and saline loading prevented the differences between the two kidneys, including PPF. In all groups GFR and renal blood flow did not differ between the two kidneys before or after AII. These data suggest that AII regulates regional blood flow in the medulla, and that the exogenously administered AII induces papillary ischemia, which serves to preserve medullary hypertonicity, preventing an increase in PPF during saline loading, and possibly contributing to the diminished natriuretic response.

Angiotensin II↗

Inner medullary hemodynamics in dogs with aortocaval fistula.

To investigate the role of medullary hemodynamics and vasoactive hormones in sodium retention in dogs with aortocaval fistula, we examined papillary plasma flow (PPF), solute content, and renal output of renin, norepinephrine, and prostaglandin E2 (PGE2) in anesthetized normal and fistula dogs. During hydropenia, cardiac output was elevated and systemic vascular resistance reduced in fistula dogs, accompanied by markedly increased renal output of renin, norepinephrine, and PGE2. In fistula dogs the blunted diuretic and natriuretic response to saline loading was not due to impaired myocardial contractility. During hydropenia and after saline loading, glomerular filtration rate (GFR) and renal blood flow were similar in normal and in fistula dogs; however, PPF was significantly lower in fistula dogs, accompanied by significantly greater papillary tissue osmolality and sodium content. These findings indicate that in fistula dogs enhanced medullary sodium reabsorption is associated with decreased PPF and stimulation of the renin-angiotensin and adrenergic nervous system. Furthermore, the reduced PPF obviates medullary solute washout during saline loading, and may contribute to the blunted diuretic and natriuretic response.

Animals↗

Managing hypertension in chronic renal disease.

Hypertension is very common in the elderly patient with renal insufficiency and may be primary or secondary to the kidney disease. In these patients, hypertension is usually associated with an increase in peripheral vascular resistance and salt sensitivity (the latter related to the degree of renal failure.) Therapy should be tailored to the individual patient, particularly when the elevated blood pressure and renal insufficiency are associated with other significant medical problems. Most of the drugs used in younger hypertensives may be used in the elderly patient with renal insufficiency, but in general, starting and maintenance doses should be lower because of the greater sensitivity due to age and/or the renal failure. The goal in the elderly hypertensive patient with renal failure is similar to that in other hypertensive patients: blood pressure should be brought to 140/90 mm Hg or lower. In the elderly patient with resistant hypertension or who manifests a decrease in kidney function as blood pressure is lowered, an effort must be made to look for associated renovascular disease.

Adrenergic alpha-Agonists↗

New concepts in acute renal failure.

The clinical patterns of acute renal failure have changed in the past 10 to 15 years. Nonoliguric acute tubular necrosis has become more common, as has nephrotoxic acute tubular necrosis. Other syndromes that have increased in incidence are acute tubular necrosis secondary to rhabdomyolysis and acute renal failure secondary to nonsteroidal anti-inflammatory drugs. Calculation of the fractional sodium excretion or the renal failure index helps distinguish between prerenal azotemia and acute tubular necrosis. In a significant number of patients with acute renal failure, a kidney biopsy may be necessary to establish the correct diagnosis and initiate the appropriate therapy.

Acute Kidney Injury↗

Sorbent recycling of ultrafiltrate in man--a 45-week crossover study.

Chronic hemofiltration as a treatment for end stage renal disease has been shown to have several advantages over standard hemodialysis including: improvement in well being, increased strength, decrease in hypotensive episodes during treatment and decrease in the degree of hypertension between treatments. The major drawback of hemofiltration as practiced today is the need to replace the large quantities of ultrafiltrate formed with sterile, pyrogen-free replacement solution. We have solved this problem by passing the ultrafiltrate through a sterile REDY Sorbent Cartridge to remove urea, creatinine and "uremic toxins" prior to returning it to the patient via a closed system. We have called this system SRUF for Sorbent Recycling of Ultrafiltrate and have carried out an A-B-A, B-A-B cross-over study (15 week periods) comparing SRUF with standard hemodialysis in 8 ESRD patients previously treated with hemodialysis. Clinical and laboratory parameters measured included: hemoglobin, hematocrit, blood transfusion requirement, electrolytes, aluminum levels, liver function tests, enzymes, lipids, glucose, cardiac function studies, weight, blood pressure, urea generation, urea space, incidence of hypotension and muscle cramps, and questionnaires on well being. The results of these studies can be summarized as follows: SRUF can be performed by the hemodialysis staff as a routine, outpatient procedure for ESRD patients utilizing the machinery and tubing developed as part of this protocol. SRUF, when used as a chronic treatment for ESRD patients, has no deleterious effects and is associated with many of the same benefits ascribed to routine hemofiltration, including improvement in well being, decrease in cramping and decrease in symptomatic hypotension during treatment as compared to hemodialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adsorption↗

Contribution of angiotensin to the control of medullary hemodynamics.

The unique architecture and organization of medullary vasculature permit regional regulation of medullary hemodynamics by vasoactive hormones and are conducive to the operation of the countercurrent multiplication system. Recent studies suggest that an increase in inner medullary blood flow causes medullary solute washout, which in turn decreases passive sodium transport in the thin ascending limb of Henle's loop. In canine models of chronic sodium retention accompanied by activation of the renin-angiotensin system, glomerular filtration rate (GFR), renal blood flow (RBF), and intracortical blood flow distribution were similar to those in normal dogs; however, papillary plasma flow (PPF) was markedly reduced and papillary tissue solute content was increased significantly both during hydropenia and after saline loading. During euvolemic diuresis with loop diuretics, there was an increased renin release associated with a marked reduction in PPF, despite an increase in total RBF. Direct intrarenal infusion of angiotensin II (AngII) (at a dose not affecting GFR and RBF) induced ipsilateral sodium retention, conservation of urinary concentration, and papillary ischemia. These studies provide evidence for regional regulation of medullary hemodynamics by AngII, possibly contributing to sodium retention in chronic salt-retaining states.

Angiotensin II↗

Minoxidil, nadolol, and a diuretic. Once-a-day therapy for resistant hypertension.

We tested a once-a-day antihypertensive regimen using minoxidil, nadolol, and a diuretic in 55 patients with resistant hypertension. Forty-seven patients had evidence of end-organ damage. Twelve had mild renal insufficiency (serum creatinine concentration, 2.5 +/- 0.3 mg/dL). In 34 patients, treatment with nadolol and a diuretic was started with minoxidil added one to four weeks later. In the remainder, minoxidil, nadolol, and a diuretic were begun simultaneously because of severe hypertension. Initial supine and standing blood pressure (BP) in the 55 patients were 186 +/- 4/111 +/- 2 and 180 +/- 4/108 +/- 2 mm Hg, respectively. After 7 +/- 1 weeks, BP was controlled in 46 patients (84%) with the supine and standing BP reduced to 140 +/- 3/80 +/- 1 and 134 +/- 3/80 +/- 1, respectively. In six patients, BP was controlled but intolerable side effects occurred, making the regimen therapeutically successful in 40 patients (73%). The BP remained controlled during a follow-up of 43 +/- 5 weeks. In 31 patients, BPs measured 24 hours after the last dose were not different from random measurements. Mean serum creatinine levels remained stable in the 12 patients with renal insufficiency.

Adult↗

Inner medullary hemodynamics in chronic salt-depleted dogs.

The effects of chronic salt depletion on medullary hemodynamics remain unknown. In the present study, sodium excretion, renal hemodynamics including papillary plasma flow, measured by the albumin-accumulation technique, and papillary tissue solute content were determined during hydropenia in 13 anesthetized sodium-replete and 10 sodium-depleted dogs. Salt depletion induced a significant rise in plasma renin activity and aldosterone without potassium depletion. Mean arterial pressure, GFR, and renal blood flow were similar in sodium-depleted and sodium-replete dogs. Despite a similar distribution of cortical blood flow (measured by the microsphere method) in the two groups, papillary plasma flow was markedly reduced in sodium-depleted dogs (8.8 +/- 1.7 vs. 22.8 +/- 1.9 ml X min-1 X 100 g-1 in sodium-replete dogs), associated with a significant decrease in renal sodium excretion. Furthermore, papillary osmolality and sodium concentration were significantly greater in sodium-depleted dogs. Ultrastructure examination revealed smooth muscle cells surrounding the efferent arterioles and pericytes with contractile potential encircling descending vasa recta. These results suggest that included in the complex hemodynamic adjustment to chronic sodium depletion is a significant reduction in inner medullary blood flow that may be important in maintaining enhanced papillary solute concentration. In addition, the anatomy of the medullary vasculature is compatible with regional regulation of medullary blood flow.

Animals↗