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The structure and function of C- and A-fibres have been studied 3 - 12 months following a single 30 min exposure of the saphenous nerve of adult rats to 1% capsaicin. Examination of nerve cross-sections showed that the number of C-fibres was reduced by 36%, but A-fibres were unaffected. The remaining C-fibres included many that were unusually small in size. The changes were not restricted to the treatment site but were found over at least a further 10 mm proximal and distal to it. In treated nerves, the C-fibre component of the compound action potential was reduced in size relative to the Aalphabeta component. Single unit studies revealed that an unusually high proportion of C-fibres had no cutaneous receptive field (54%, compared with 28% in controls). There was no such change for A-fibres. The conduction velocity range for C-fibre units in treated nerves was almost normal, but this sample contained an unusually low proportion of polymodal nociceptors. Allowing for the fall in total numbers and the reduction in units with cutaneous receptive fields, it was calculated that overall the numbers of C-polymodal nociceptor units had fallen by 74%. No significant changes in number had occurred in the other classes of C-afferents. The reduction in the numbers of nociceptive C-fibres is likely to be the direct cause of the reduction in pain responses and in neurogenic inflammation that several groups have reported following treatment of adult rats with capsaicin. Reduction in the numbers of C-fibre is also likely to be the reason for reduced neuropeptide levels seen in tissues innervated by treated nerves.

The aim of the study was to assess the usefulness of 24-hour blood pressure (BP) and heart rate (HR) monitoring in patients with "resistant" hypertension. 30 patients (44.1 +/- 9.9 years) with diastolic BP 100 mm Hg or more in spite of treatment with three or more antihypertensive drugs were studied. Ambulatory recording of BP and HR was performed by means of Del Mar Avionics monitoring system 9000. Mean recording time was 21.5 hours and mean number of measurements during one recording--56.7. Mean ambulatory systolic and diastolic BP values were significantly lower than mean value of three casual measurements (146.0 +/- 24.6 vs 171.5 +/- 21.2 mm Hg for systolic and 97.2 +/- 11.3 vs 110.4 +/- 7.5 mm Hg for diastolic BP p less than 0.01) In 14 (46.6%) systolic BP and in 10 patients (33.3%) diastolic BP were normal. The patients with normal and abnormal ambulatory BP recordings did not differ in regard to age and mean clinic BP levels. However, patients with abnormal ambulatory BP recordings were more often overweight and showed a greater frequency of left ventricular hypertrophy and family history of hypertension and its complications. The results of the study show that ambulatory BP monitoring may be of value in assessing the response to antihypertensive treatment in patients with so called resistant hypertension as judged on the basis of clinic pressure.

This study investigated the validity of an experimental video examination that had previously been shown to be feasible and have reproducible scores for a sample of candidates taking the 1987 ABIM Cardiovascular Disease examination. Correlations of the three video formats of echocardiograms, ventriculograms, and arteriograms with traditional item formats, similar content multiple choice question scores, experience, and external measures suggest that the video formats could be a worthwhile addition to the examination.

Extracts containing renal erythropoietic factor (REF) and others which contain renin reportedly enhance erythropoietin (Ep) titers in the plasma of hypoxic nephrectomized rats. Studies reported here were designed to elucidate the mechanism by which renin increases Ep production in the anephric rat. Injection of a renal extract containing renin significantly raised the blood pressure of anephric rats, and when it was injected just prior to exposure to hypoxia and 15 hour postnephrectomy, the resultant plasma Ep level exceeded that observed in rats exposed to the same hypoxic conditions immediately postnephrectomy. In contrast rats made hypoxic 15 hours after nephrectomy, but not given renin, had plasma Ep levels which were lower than those of anephric rats made hypoxic immediately postoperatively. When renin was injected immediately after nephrectomy or into normal rats, it failed to stimulate Ep production. When diazoxide was injected with the renin extract into hypoxic nephrectomized rats, the vasopressor effect of renin was abolished for 4 hours, and the plasma Ep levels were significantly lower than those of hypoxic nephrectomized animals injected only with renin, Injection of angiotensin II into anephric, hypoxic rats had an effect comparable to that of renin on extrarenal Ep roduction. REF was not detectable in the renin preparation. These results are best explained by the concept that renin and angiotensin increase extrarenal Ep production by causing vasoconstriction and consequently hypoxia in extrarenal sites of Ep production. Also of interest is the finding that plasma EP levels of rats, injected with renin and made hypoxic 15 hours postnephrectomy, are higher than those previously reported to occur in anephric rats.

The functional expression of papillary necrosis was investigated with a model of drug-induced papillary necrosis. Bromoethylamine hydrobromide (BEA) administration to rats uniformly resulted in the development of papillary necrosis. All studies were performed 24 hours after BEA administration with the exception of the electrolyte balance studies, which were performed during the 72 hours after the induction of papillary necrosis. GFR was not different between BEA-treated and sham rats. BEA-treated rats had a significantly lower maximal urine osmolality and free water reabsorption than did sham rats. Renal tissue concentrations of sodium, potassium, and water were not different between BEA-treated and sham rats. During water diuresis, free water clearance was not significantly different between the two groups. During sodium bicarbonate administration, maximal bicarbonate reabsorption and urine-blood Pco2 gradient (at comparable urine bicarbonate concentrations) were not significantly different between the two groups. During sodium sulfate infusion, there was no difference in minimum urine pH, ammonium excretion, and net acid excretion between chronically acidotic BEA-injected and sham rats. In rats on "zero" sodium intake, BEA administration resulted in a significant increase in urine flow and sodium excretion, whereas sham rats remained in sodium balance. In rats with restriction of both sodium and chloride, BEA administration resulted in a significant wastage of sodium, chloride, and calcium. There was no difference in potassium excretion between BEA-treated and sham rats during hydropenia, bicarbonate administration, sodium sulfate infusion, or ingestion of a normal potassium diet. When potassium intake was restricted to "zero," BEA-treated rats developed potassium wastage; when potassium intake was increased to 21 mEq/day, BEA-treated rats had a significantly lower potassium excretion than did sham rats. These findings may result from alterations in collecting duct transport, but damage to deep medullary structures may also contribute.

Several studies have suggested that increased activity of the renin-angiotensin system plays an important role in the pathogenesis of acute renal failure. An analog of angiotensin II, 1-sarcosine, 8-leucyl angiotensin II (AIIA), a potent antagonist of the pressor response of angiotensin II (AII), was injected (16 mug/200 gm) or infused (1.5 mug/200 gm/min) intravenously into glycerol treated (8 ml/kg) rats to evaluate the involvement of the renin-angiotensin system as a mediator in the pathogenesis of acute renal failure. Dehydrated animals, whether untreated, given AIIA, or saline became progressively azotemic and died with 72 hours after glycerol administration. Plasma renin activity, as measured by radioimmunoassay, decreased below dehydrated control levels at one hour after glycerol administration (7.45 ng/ml/hr +/- 1.29 (SE) to 3.24 +/- 0.64), and progressively increased to a maximum 9.9 +/- 0.98) at 17 hours; there was no difference between dehydrated control levels and those obtained 24 and 48 hours after glycerol. Nondehydrated glycerol treated rats were studied as above. These animals developed a non-lethal form of acute renal failure, the severity of which was also unaffected by AIIA administration. These observations indicate that AIIA neither prevents nor alters the development of glycerol induced acute renal failure.

Receptive field parameters of G- and D-hair units were investigated in adult rats given capsaicin as neonates. An air jet stimulator mounted on a two-way micromanipulator was used for accurate mapping of receptive fields. Diameters of G- and D-hair unit receptive fields were similar in both control and treated groups averaging 2.14 and 2.44 mm respectively with a 1.5 X threshold stimulus. It is concluded that the reported expansion of rat spinal cord cutaneous receptive fields following capsaicin treatment does not have any significant peripheral component.

By examination of compound action potentials in the saphenous nerve of the anaesthetized rat it has been shown that capsaicin causes a rapid, dose-dependent, failure of conduction in many C-fibres when applied directly to the nerve. A large reduction in C-fibre conduction occurs with concentrations as low as 110 microM. After a 15-30 min exposure to capsaicin, only partial recovery occurs in 1 h. Similar block of C-fibre conduction occurs in the ferret. However, only smaller, reversible, reductions in C-fibre conduction were seen in the guinea-pig and rabbit, even at the highest concentration of capsaicin used (33 mM). A small reduction in the A delta component of the compound action potential occurred in all four species. In the rat and ferret the effects were much less than those on C-fibres. At high doses, small reversible effects were also seen on the fastest conducting A alpha beta component of the compound action potential in the rat, rabbit and guinea-pig; no effects were seen on the A alpha beta fibres in the ferret. Decreases in amplitude of the compound action potential were accompanied by some slowing of conduction in most cases. The slowing was less than 5% except for the rat A alpha beta and C-fibres and the ferret C-fibres where 9-15% changes occurred at the highest doses of capsaicin. Opening the connective tissue sheath of the nerve did not significantly increase the effectiveness of capsaicin.

Previous studies demonstrated that acute infusion of cuprophan activated plasma into experimental animals produce cardiopulmonary changes which included severe pulmonary hypertension. It was further suggested that these changes were mediated by complement activation products. The current study examined the role of arachidonic acid metabolites in the pathogenesis of cuprophan-induced pulmonary hypertension in the swine. Plasma thromboxane concentrations and pulmonary arterial pressure rose concomitantly with cuprophan-activated plasma infusion; both could be inhibited by the specific thromboxane synthetase inhibitor, OKY1581. Likewise, this inhibitor also blocked the increment in plasma thromboxane concentrations and pulmonary arterial pressure induced by zymosan-activated plasma. In vitro incubation of cuprophan-activated plasma with porcine lung fragments produced significantly higher thromboxane concentrations in the medium than incubation with other porcine tissues examined. It is postulated that the complement activation products formed in the plasma during cuprophan exposure subsequently stimulated release of thromboxane from the lungs and other tissues upon infusion of the plasma into animals. The thromboxane, in turn, triggers the pulmonary hypertension.

The purpose of this study was to examine proximal and distal tubular function in rats with nonoliguric, myohemoglobinuric acute renal failure (ARF). ARF was induced with glycerol (50%, 10 ml/kg of body wt, i.m.), and renal function was studied 24 hours after glycerol or saline (controls) injection. Glycerol injection caused a 50 to 90% depression in GFR and a significant rise in blood urea nitrogen concentration. Animals with ARF exhibited glycosuria with normal blood sugar levels and a striking depression in tubular glucose reabsorption per milliliter of GFR. The capacity to reabsorb (mEq/liter GFR) was intact at normal blood bicarbonate levels, but was markedly depressed when blood bicarbonate was raised. The tubular maximum for para-aminohippurate (PAH) secretion and the renal extraction fraction of PAH were strikingly depressed in rats with ARF. Distal acidification as assessed by the urine-to-blood gradient of PCO2 (UB PCO2) was normal both during maximal alkalinization of the urine with bicarbonate (urine pH, approximately 7.8) or during neural phosphate infusion (urine pH, approximately 7.0). Net acid excretion per milliliter GFR and minimal urine pH (less than 5.5) following 3 days of ammonium chloride ingestion was similar in control and ARF animals. Potassium excretion was intact in maximal urinary osmolality were significantly altered in animals with ARF. Cortical and outer medullary Na-K-ATPase specific activities were significantly depressed in ARF rats. This occurred as a consequence of enzyme loss and not secondary to alterations in enzyme kinetics of absolute tubular sodium reabsorption. Light and electron microscopy showed diffuse proximal tubular damage, whereas glomeruli and distal tubules were intact. These data demonstrate that glycerol injection produces a diffuse proximal tubular transport defect associated with histologic and enzymatic alterations.

We previously demonstrated that intrarenal angiotensin II generation during glycerol-induced acute renal failure was attenuated, which may have resulted from the inability of intrarenal converting enzyme to convert renal angiotensin I to angiotensin II. In order to test this hypothesis in vivo, we determined the ability of the kidney to convert angiotensin I to angiotensin II by measuring the decrease in renal cortical blood flow (RCBF) in response to exogenous angiotensin I administration. Changes in RCBF were monitored by laser-Doppler velocimetry. Three groups of rats were studied: Group I, controls (N = 7); 24 hours prior to study Group II animals were injected with 50% glycerol, 8 ml/kg i.m. (N = 4); and Group III rats were injected with mercuric chloride, 3 mg/kg s.c. (N = 5). All experimental animals had a three- to sixfold rise in serum creatinine. Mean glomerular filtration rate (GFR) of the left and right kidney in control rats was 0.7 and 0.7 ml/min, respectively. Twenty-four hours after glycerol, GFR was 0.2 ml/min in the left kidney and 0.2 ml/min in the right kidney. In HgCl2 treated rats GFR was 0.1 ml/min in the left kidney and 0.1 ml/min in the right kidney. Each of the following maneuvers elicited a similar rise in blood pressure in Groups I through III. Specifically, when first angiotensin I (4 micrograms/kg/min) was infused for three minutes; second, when 10 minutes later angiotensin I (5 micrograms) was directly applied on the left kidney; and third, when angiotensin II (5 micrograms) was topically administered.(ABSTRACT TRUNCATED AT 250 WORDS)

Patients and/or experimental animals with chronic renal failure have decreased serum levels of triiodothyronine (T3), a hormone well known for its erythropoietic activity. The following studies were designed in order to determine whether this observed abnormality in T3 metabolism is an important contributory factor to the etiology of the anemia of uremia. Groups of rats were made chronically uremic by a standard 5/6 nephrectomy technique and received slightly above physiological doses of T3 either by intermittent S.C. injections (twice daily) or by continuous infusion from intraperitoneally implanted osmotic minipumps. After 2 weeks of such treatment, and despite a normalization of serum T3 levels, there were no significant changes in the hematocrit, individual red cell mass, or serum erythropoietin levels of the uremic animals given T3 compared to control rats. We conclude that (1) the decreased serum T3 levels observed in uremia are not an important contributory factor to the pathogenesis of the anemia, and (2) treatment with replacement doses of T3 does not result in significant improvement of erythropoiesis.

Primary cultures of atrial and ventricular myocytes (approx. 1 x 10(5) cells/culture) were prepared from adult teleost fish Gila atraria and maintained for 10 days. Immunoreactive atrial natriuretic peptide (ir-ANP) from fish atrial and ventricular cells was 3.9 and 2.8 ng/culture respectively, values not significantly different. Atriocytes from rat and mouse secreted comparable amounts of ANP which were not significantly different from atrial fish cultures (5.2 and 4.3 ng/culture). In contrast, their ventricular myocytes secreted only small quantities of ANP (0.8 and 0.3 ng/culture). When analyzed by reversed-phase HPLC, the media of both fish atrial and ventricular myocytes contained a peptide which exhibited properties similar to authentic human ANP (Ser 99-Tyr 126), suggesting a significant degree of sequence homology between fish and mammalian ANP. Fish ventricular cells, unlike normal mammalian ventricular cells, secrete substantial quantities of immunoreactive-ANP.

The effects of the angiotensin converting enzyme (ACE) inhibitor enalapril on the proteinuria and degree of focal glomerular sclerosis hyalinosis (FSH) in chronic puromycin aminonucleoside nephropathy (PAN) were examined. Chronic PAN was induced in male Sprague-Dawley rats by seven subcutaneous injections of puromycin aminonucleoside (20 mg/kg) over 10 weeks (Groups I and II). Group II rats also received enalapril 10 mg/kg/day in the drinking water throughout the study (12 weeks). Group III rats served as age-matched controls. Proteinuria was similar in Groups I and II (35.5 +/- 9.7 versus 29.1 +/- 4.1 mg protein/mg creatinine, mean +/- SEM, P greater than 0.05). Serum creatinine remained unchanged in Group I, but rose from 0.7 +/- 0.04 to 1.2 +/- 0.1 mg/dl (mean +/- SEM, P less than 0.05) in Group II. FSH was 13.8% in Group I, 12.9% in Group II (P greater than 0.05), and 0.6% in Group III. There was no significant difference in glomerular lipid content and in immunofluorescence for rat albumin, fibrinogen, IgM, IgG, and C3 between Groups I and II. ACE activity was inhibited by 94% in serum, 83% in lungs, and 92% in kidneys; and blood pressure response to. Angiotensin I challenge was decreased by 50% in rats similarly treated with enalapril versus controls. In summary, proteinuria and glomerular sclerosis in this model are not affected by ACE inhibition.

The purpose of this paper was to assess the reproducibility of three simulations presented on videotape: echocardiograms, ventriculograms, and arteriograms. The results indicate that roughly comparable numbers of cases, but different amounts of testing time, are required to achieve specified levels of reproducibility; score interpretation affected reproducibility in the expected ways.