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Biomedical subjects

J C McGiff

Publications and source records attributed to J C McGiff.

At least 19 recordsLinked to original sources
PubMed1979

6-Keto-prostaglandin E1 inhibits the aggregation of human platelets.

6-Keto-prostaglandin E1 (6-keto-PGE1) was found to have a similar potency to prostacyclin (PGI2) as an inhibitor of platelet aggregation. It caused a time and concentration dependent inhibition of ADP, collagen and epinephrine induced platelet aggregation, the dose ratios for 70% inhibition by 6-keto-PGE1, PGI2 and PGE1 being approximately 1 : 1 : 13. In doses similar to those of PGI2, 6-keto-PGE1 partially inhibited the release of [3H]-serotonin from platelet-rich plasma induced by collagen.

Collagen↗
PubMed1979

Hypotensive and renovascular actions of 6-keto-prostaglandin E1, a metabolite of prostacyclin.

Either intra-aortic or intravenous injections of a stable prostaglandin metabolite, 6-keto-prostaglandin E1 (6-keto-PGE1), caused similar dose-dependent falls in blood pressure and reductions in renovascular resistance in the anesthetized rat. The threshold dose was 0.3 microgram/kg. A maximum hypotensive effect occured at 10 micrograms/kg, but renal blood flow was further reduced by a dose of 30 microgram/kg. 6-keto-PGE1, like prostacyclin, could be a circulating hormone.

Animals↗
PubMed1979

Comparison of effects of prostaglandins E2 and I2 on rat renal vascular resistance.

Effects of PGE2 and PGI2 on renal vascular resistance (RVR) were compared in anesthetized rats. Renal blood flow and systemic blood pressure were measured before and during infusion of PGE2 (2--2 microgram/min) or PGI2 (1--5 microgram/min) into the aorta just proximal to the renal arteries. Both prostaglandins significantly decreased blood pressure and renal blood flow, but effects on RVR were dissimilar. At low doses, PGI2 reduced RVR in 8 of 10 rats; PGE2 increased it in 5 of 7. At higher doses, PGE2 increased RVR in all rats; during PGI2 infusion RVR did not significantly exceed control at any dose. We conclude that, in the intact rat, PGE2 increases RVR either directly or through potentiation of other constrictor stimuli, while PGI2 tends to reduce RVR and diminish the renal response to other constrictor stimuli. PGI2 is the only prostaglandin found to decrease RVR in the rat.

Animals↗
PubMed1979

Metabolism of prostacyclin in the rabbit kidney.

In the isolated rabbit kidney perfused with Tyrode's solution, we examined the metabolism of radiolabeled prostacyclin. [9-3H]Prostacyclin was infused into the kidney and the radiolabeled products from the renal venous effluent were separated by thin layer chromatography and identified by gas chromatography-mass spectrometry. The major products were 7,9-dihydroxy-4,13-diketo-dinor-prostanoic acid and dinor-6-keto-prostaglandin F1alpha. They represented 25% and 10% of the total radioactivity, respectively. Metabolism of prostacyclin by the kidney may be an important determinant of the effects of prostacyclin on renal function.

Animals↗
PubMed1979

Effect of indomethacin on blood pressure in the normotensive unanaesthetized rabbit: possible relation to prostaglandin synthesis inhibition.

1. To test the hypothesis that endogenous prostaglandins contribute to the regulation of blood pressure, we studied the effect of an inhibitor of prostaglandin synthesis, indomethacin, on mean aortic blood pressure in the normotensive, unanaesthetized rabbit. 2. Daily administration of indomethacin at 42 mumol/kg subcutaneously, but not of vehicle only, for 14 consecutive days, elevated the average mean arterial pressure in seven rabbits from 88 +/- 3 mmHg on the last day of the control period to 105 +/- 3 mmHg (P less than 0.01) and 107 +/- 2 mmHg (P less than 0.01) on days 6 and 14 of indomethacin treatment respectively, and reduced the urinary excretion of prostaglandin-like substance from 1.06 +/- 0.26 to 0.17 +/- 0.05 nmol of prostaglandin E2 equivalents/day (P less than 0.05; n = 5). Neither indomethacin nor the vehicle affected the intake of water, the 24 h urine volume, the cumulative difference between sodium intake and urinary sodium excretion, or the plasma volume. 3. The results of the study are compatible with the hypothesis that one or more prostaglandins contribute to maintain normotension in the rabbit and that reduction in prostaglandin biosynthesis may cuase blood pressure to rise.

Animals↗
PubMed1979

Compartmentalization of prostaglandins and prostacyclin within the kidney: implications for renal function.

When renal function is compromised, the circulation to the kidney is sustained by a major prostaglandin component, withdrawal of which results in significant hemodynamic effects, particularly reduction in blood flow to the inner cortex and medulla. Prostaglandins modulate the effects of vasoactive hormones by attenuating the renal actions of the renin-angiotensin system and contributing to and, perhaps, mediating some of those of the kallikreinkinin system. In addition, a prostaglandin mechanism, presumably located in the renal arterioles, participates in the regulation of renin release. Although cyclooxygenase is present in several renal tissues, the major products of arachidonic acid metabolism may be tissue specific and, consequently, their effects may be primarily restricted to one compartment, e.g., the proposed interaction of prostacyclin and renin within the vascular pole of the glomerulus; and PGE2/PGF2a with the kallikrein-kinin system within the urinary compartment. The former is related to the regulation of renin release and renal vascular resistance and the latter to the excretion of water and perhaps salt.

Animals↗
PubMed1979

Prostacyclin effects on renal hemodynamic and excretory functions in the rat.

Blood pressure, renal blood flow, glomerular filtration rate and urine composition and flow rate were measured, and renal vascular resistance was calculated, before and during infusion of prostacyclin (PGI2) i.v. or i.a. just proximal to the origins of 250 ng/min, PGI2 caused a significant but slight (13%) reduction in renal vascular resistance, but did not consistently increase renal blood flow. Given at the highest infusion rate which could be sustained without reducing blood pressure, PGI2 did not alter glomerular filtration rate or urine composition or flow rate. Intravenous PGI2 infusion caused reductions in systemic blood pressure and renal blood flow at a dose of 50 ng/min; infusion into the abdominal aorta produced equal reductions in pressure and flow at a dose of 500 ng/min. Although PGI2 is the only prostaglandin shown to reduce renal vascular resistance in the rat, it does not appear to be sufficiently specific for the renal vasculature or potent enough to justify suggesting a physiological role in regulation of renal function in the rat.

Animals↗
PubMed1978

Metabolism of prostacyclin in blood vessels.

The activity of 15-hydroxyprostaglandin dehydrogenase has been shown to be high in both mesenteric arteries and veins; the present study suggests that it may be responsible for the inactivation of prostacyclin (PGI2). The cytoplasmic fractions of bovine mesenteric arteries and veins were incubated with radiolabeled PGI2 in the presence of NAD+ or NADP+. The substrate was rapidly converted to a product, which was isolated and identified as 6,15-diketo prostaglandin F1alpha, (6,15-diketo-PGF1alpha) by thin layer chromatography and gas chromatography-mass spectrometry. The initial reaction rate began to level off after less than 1 min of incubation at 37 degrees C. When radiolabeled 6-keto-PGF1alpha, the stable hydrolysis product of PGI2, was used as substrate under the same conditions, 97% was recovered unmetabolized after 2 min of incubation. Catabolism of PGI2 may be a major determinant of its levels in blood vessels and, therefore, may be of crucial importance to regulating the action of PGI2. Further, estimation of PGI2 generation by either tissues or organs may be misleading if only 6-keto-PGF1alpha is measured.

6-Ketoprostaglandin F1 alpha↗
PubMed1978

Endogenous prostaglandin synthesis inhibitor in the renal cortex. Effects on production of prostacyclin by renal blood vessels.

1. The capacity of various tissues of the porcine kidney to convert [1-14C]arachidonic acid into radiolabelled prostaglandins was studied. 2. Only after removal from the cortical matrix, were renal blood vessels able to convert arachidonic acid into prostaglandins (primarily prostacyclin). In contrast, convoluted tubules showed a low capacity to metabolize arachidonic acid. 3. The failure to demonstrate prostaglandin synthesis by renal cortical slices is related to the presence of an inhibitor of cyclo-oxygenase. Thus the addition of renal cortical incubate to isolated vascular tissues and ram seminal vesicles inhibited their ability to synthesize prostaglandins. 4. Slices of renal medulla metabolized arachidonic acid primarily to prostaglandin F2alpha; lesser amounts of prostaglandin E2 and prostacyclin were generated. 5. The large capacity of the renal vasculature to generate prostacyclin is consistent with an important role for this prostaglandin in regulation of renin release and renal haemodynamics.

Animals↗
PubMed1978

Prostaglandins and renal function.

Prostaglandins modulate the effects of vasoactive hormones by attenuating the renal actions of the renin-angiotensin system and contributing to and, perhaps, mediating some of those of the kallikrein-kinin system. A prostaglandin mechanism participates in the regulation of renin and erythropoietin release. When renal function is compromised, the circulation to the kidney is sustained by a major prostaglandin component withdrawal of which results in significant hemodynamic effects, particularly reduction of blood flow to the inner cortex and medulla.

Animals↗
PubMed1978

Effects of aldosterone and deoxycorticosterone on the urniary excretion of kallikrein and of prostaglandin E-like substance in the rat.

Deoxycorticosterone (5 mg) and aldosterone (0.25 mg), given to rats for 14 days, increased the urinary excretion of kallikrein and of prostaglandin E-like substance and produced polyuria, but affected neither sodium excretion nor blood pressure. These results suggest that interactions of mineralocorticoid hormones, kinins and of prostaglandins may be important in the maintenance of salt-water homeostasis.

Aldosterone↗
PubMed1978

Interrelations of the renal kallikrein-kinin system and renal prostaglandins in the conscious rat. Influence of mineralocorticoids.

To investigate possible relationships between mineralocorticoids, the renal kallikreinkinin system, and renal prostaglandins, we studied the effects of aldosterone and deoxycorticosterone acetate (DOCA) and of an inhibitor of kallikrein, aprotinin, on the urinary excretion of kallikrein and prostaglandin E-like substance (PGE) by the conscious rat. Aldosterone (0.25 mg/day, sc), injected into six rats for 14 consecutive days, increased PGE and kallikrein excretion from 52.3 +/- 8.7 (mean +/- SE) ng/day and 29.8 +/- 3.0 U/day to 141.5 +/- 30.7 ng/day (P less than 0.02) and 105.6 +/- 28.1 U/day (P less than 0.05), respectively. Similarly, injections of DOCA (5 mg/day) into 14 rats increased the excretion of PGE and kallikrein, measured before and after 10 days of treatment, from 41.6 +/- 3.9 ng/day and 39.4 +/-4.9 U/day to 194.3 +/- 20.7 ng/day (P less than 0.001) and 90.6 +/- 14.7 U/day (P less than 0.001), respectively. Injections of aprotinin for 4 days (50,000 KIU twice daily, sc) in conjunction with DOCA into eight rats pretreated with the steroid for 10 days decreased the urinary excretion of kallikrein and PGE, measured on the 4th day of aprotinin administration, by 61% (P less than 0.01) and 80% (P less than 0.001), respectively. Urinary potassium excretion decreased throughout the course of aprotinin treatment, whereas sodium excretion and urine volume decreased during the first 2 days but subsequently returned toward control values. This study demonstrates that mineralocorticoids enhance the urinary excretion of PGE, and this effect appears to be a consequence of activation of the renal kallikrein-kinin system by the steroids. Thus, changes in the intrarenal activity of the kallikrein-kinin system may modulate renal prostaglandin release.

Aldosterone↗
PubMed1977

Synthesis of prostaglandins by the ductus arteriosus of the bovine fetus.

Previous studies demonstrated that prostaglandins are local or tissue hormones which can be released from blood vessel walls. In the present study, we investigated the capacity of bovine ductus arteriosus to synthetize prostaglandins in vitro. After incubation of slices of ductus arteriosus in Krebs' solution with (1-14C) arachidonic acid for 3 hours, more than 40% of the radiolabeled material recovered from the incubating medium were metabolites of arachidonic acid. The major product was indistinguishable from 6 keto-PGF1alpha as determined by its chromatographic motility and resistance to alkaline conversion to PGB. The PGI2 synthetic capacity of the ductus arteriosus, as revealed by the predominance of its major metabolite 6 keto-PGF1alpha, suggests that this metabolic pathway of arachidonic acid may contribute to the hemodynamic changes occurring during fetal life and at birth.

Animals↗
PubMed1977

Contribution of prostaglandins to the renal circulation in conscious, anesthetized, and laparotomized dogs.

The effects of an inhibitor of prostaglandin (PG) synthetase, indomethacin, were studied on renal blood flow (RBF) and mean aortic blood pressure (MABP) and related to changes in concentrations of PGs in renal venous blood under widely different experimental conditions. Although levels of PGE-like material ("PGE") in renal venous blood of the chloralose-anesthetized-laparotomized dog were 8-fold greater than in conscious dogs, viz., 0.39 vs. 0.05 ng/ml of blood, respectively, RBF and MABP were similar for each group. Indomethacin in doses as high as 10 mg/kg, iv, affected neither RBF, MABP, nor PG levels either in the conscious dog or in the anesthetized dog. However, in the anesthetized-laparotomized dog, smaller doses of indomethacin (2 mg/kg, iv) decreased RBF by more than 40% and increased MABP by 15%. This was associated with a decline in concentration of renal venous PGs to those levels observed in conscious dogs. The principal renal PG varied according to the experimental conditions. The venous levels of "PGF" were greater than "PGE" in conscious dogs, whereas in acutely stressed dogs the renal venous concentrations of "PGE" were more than 2-fold those of "PGF". Plasma renin activity was highly correlated with "PGE" levels in renal venous blood, but not with "PGF" levels. Thus, in the acutely stressed dog, the renal circulation is supported by a major PG component, withdrawal of which results in a decline in RBF. In contrast, in the conscious dog at rest, renal PGs do not appear to contribute significantly to RBF. The significance of the small basal release of PGs into the renal venous effluent of the conscious dog, which is not affected by indomethacin, remains to be determined.

Anesthesia↗