Search PubMed⌕ Search

Biomedical subjects

R J Workman

Publications and source records attributed to R J Workman.

28 records · Page 2Linked to original sources
PubMed1980

Renin and prorenin in hog brain: ubiquitous distribution and high concentration in the pituitary and pineal.

With the objective of clarifying the nature of renin-like activity in the brain, we have devised methods to distinguish true renin from acid protease. These methods were used to determine the regional distribution of true renin in hog brain. The pineal was found to be the richest source of renin followed by the adenohypophysis and choroid plexus. The hypothalamus, cerebellum and amygdala contained moderately high concentrations of renin. Renin concentration in the neurohypophysis was negligible. Many regions contained activatable prorenin. The molecular weight and the pH-dependence of the brain renin were identical to these same properties of renal and plasma renins. Based upon its specific affinity to concanavalin A, brain renin was judged to be a glycoprotein. The electrofocusing pattern of renin from different regions of the brain differed from that of plasma and kidney renins, a discrepancy which could be interpreted as evidence for the endogenous synthesis of renin in the brain.

Angiotensin I↗
PubMed1979

Specific antibody to hog renal renin and its application to the direct radioimmunoassay of renin in various organs.

We produced anti-hog renin antibodies using as antigens pure hog renal renin that either had been insolubilized or conjugated to tetanus toxoid. High titer antibodies were obtained, which demonstrated different cross-reactivity with renins from other species. A direct radioimmunoassay for renin was developed using antibody, monoiodinated 125I-hog renin, and various methods for separating free and antibody-bound trace. This assay was capable of detecting 40 pg of hog renin and was applied to the determination of renin in hog blood and other organs. Based on the direct measurement of renin by this radioimmunoassay, the renin-like activity (i.e., the ability to generate angiotensin I from renin substrate preparations) of the pituitary gland was found to be due mostly to true renin, whereas the renin activity of other hog tissues, including the adrenal gland, liver, lung, spleen, and submaxillary gland, was not identified as renin and may have been due to cathepsins.

Adrenal Glands↗
PubMed1979

Circulating levels of angiotensin I measured by radioimmunoassay in hypertensive subjects.

The development of a uniquely sensitive and specific antiserum to AI has led to the establishment of a radioimmunoassay capable of detecting 7.5 pg of AI per milliliter of plasma. Due to its sensitivity this assay permits the measurement of circulating levels of AI, obviating many of the controversial aspects of previously described AI assays which all required either an incubation step at 37 degrees C to allow renin to catalyze the formation of sufficient AI or an extraction procedure to concentrate sufficient peptide to make quantification feasible. Since the sensitivity of this assay also depends upon the availability of very pure trace, a method is described for preparing monoiodinated 125I-AI of specific activity greater than 1000 microCi/microgram. To demonstrate the versatility and sensitivity of this assay, changes in circulating AI levels in response to physiologic stimuli were measured. Blood samples were obtained from 88 subjects from the inferior vena cava below the renal veins in both the supine and upright positions. Values ranged from 12 to 1990 pg/ml of plasma. Eighty-five of the 88 displayed a rise in the AI level during an upright tilt, the mean for the group increasing from 220 to 385 pg/ml of plasma. Three subjects had samples drawn simultaneously from the inferior vena cava and a peripheral artery and/or vein. The amounts of AI in all three sampling locations were essentially the same. Seventeen patients with essential hypertension underwent an infusion of 1.5 L of normal saline, and circulating AI levels were determined before and 120 and 150 min after the start of the infusion. All 17 experienced suppression of their AI levels, the mean for the group at 0, 120 and 150 min being 177, 55, and 50 pg/ml of plasma, respectively. Circulating AI correlated well (r = 0.87009) with plasma renin activity in 226 samples from the renal veins and inferior vena cava from individuals with hypertension of various etiologies.

Angiotensin I↗
PubMedDate not supplied

Relationship of renal hemodynamic and functional changes following intravascular contrast to the renin-angiotensin system and renal prostacyclin in the dog.

Deterioration in renal function has been observed after the use of intravascular contrast media. In an attempt to identify factors responsible for this phenomenon, meglumine iothalamate (Conray 60), in a dosage range of 2.5-3.3 ml/kg, was injected as a bolus into the aorta of dogs. Serial measurements were made of parameters of renal function as well as of changes in aortic and renal venous levels of angiotensin II, renin activity, and 6-keto-PGF1 alpha, the stable metabolite of prostacyclin. The major findings were (1) an initial, brief increase followed by approximately a 20% sustained decrease in renal blood flow and creatinine clearance, (2) no significant changes in angiotensin II and renin levels, and (3) a significant decline in the renal secretory rate of 6-keto-PGF1 alpha. These observations suggest that the suppression of prostacyclin, rather than the activation of the renin-angiotensin system, may contribute to the renal function changes attending the use of intravascular contrast media.

6-Ketoprostaglandin F1 alpha↗
PubMedDate not supplied

Thromboxane synthetase inhibitor UK38,485 lowers blood pressure in the adult spontaneously hypertensive rat.

Treatment of young spontaneously hypertensive rats (SHR) with a thromboxane synthetase inhibitor (TSI) attenuates their subsequent development of hypertension. In this study, treatment of adult SHR during the established phase of hypertension with the TSI UK38,485 (100 mg/kg daily) lowered systolic blood pressure from baseline after 4 days of treatment to a maximum depression of 25 mm Hg on day 10 of the study. Additional confirmation of the fact that this TSI does not lower blood pressure acutely was made via continuous intraarterial recordings in SHR administered their first dose of UK38,485. Urinary dinor-6-keto-PGF1 alpha excretion was measured by a highly specific chemical-ionization, negative-ion GC/MS assay in the selective ion monitoring mode. This metabolite of PGI2 was not significantly affected by 6 days of daily administration of UK38,485 to adult SHR and implies that there was not sufficient endoperoxide shunting to affect total body PGI2 production. The finding that UK38,485 exhibited antihypertensive activity during established SHR hypertension was unexpected and has considerable practical and theoretical significance.

Animals↗
PubMedDate not supplied

Immunohistochemical evidence that angiotensins I and II are formed by intracellular mechanism in juxtaglomerular cells.

The existence of angiotensin II (AII) immunoreactivity in juxtaglomerular (JG) cells of rat kidney, which has been demonstrated previously by immunohistochemical studies, can be explained either as the product of intracellular synthesis or by the internalization of receptor-bound AII originating in plasma. To resolve these two alternative mechanisms, attempts were made to identify AI in JG cells of rat kidney by immunohistochemical staining using specific antibodies to AI. Although AI-like immunoreactivity was not detected in normal rat kidney, rats treated with the angiotensin-converting enzyme inhibitors, MK-421 or captopril, showed AI-like immunoreactivity in JG cells. The presence of renin and AII-like immunoreactivity was demonstrated in the same cells by specific antibodies to respective antigens used on adjacent serial sections. These findings support an intracellular mechanism of the formation of AII and suggest an intracellular renin angiotensin system, presumably separate from the extracellular system.

Angiotensin I↗