Hypotensive effect in the rat after oral prostacyclin (PGI2)

British Journal of Pharmacology, 1983

The relationship between the blood pressure fall, induced by antihypertensive drugs or bleeding, and the formation of prostacyclin (PGI2)-like activity in the thoracic aorta of spontaneously hypertensive rats has been investigated. Inhibition of ADP-induced platelet aggregation was used to assess PGI2-like activity. 2 The decreases in blood pressure produced by clonidine, dihydralazine and prazosin were associated with increases of PGI2-like activity of 50-80%. The increase in PGI2-like activity correlated well with the blood pressure decrease, independently of the mechanism of the fall in blood pressure.

British Journal of Pharmacology, 1980

The aim of the study was to determine the mechanism of the hypotension and bradycardia produced by prostacyclin (PGI2). 2 Haemodynamic studies were carried out in nineteen open-chest beagle dogs anaesthetized with chloralose. PGI2 was infused intravenously or into the left atrium. 3 Infusions of PGI2 either intravenously or into the left atrium equally reduced arterial pressure and total peripheral resistance but bradycardia was greater after infusion into the left atrium. 4 Comparison of effects of PGI2 with those of prostaglandin E2 (PGE2) showed that although left atrial infusions both reduced aortic pressure and total peripheral resistance, PGE2 always increased heart rate, cardiac output and maximum acceleration. 5 Similar effects were observed with sodium nitroprusside except that it always caused tachycardia and reduced stroke volume. 6 Atropine (0.05 or 1 mg/kg i.v.) reduced or reversed the bradycardia induced by PGI2 but its hypotensive effects were reduced only after 1 mg/kg atropine. After vagotomy changes in cardiac output, stroke volume and maximum acceleration were increased, the hypotensive effects of PG12 were reduced and the bradycardia was reversed; effects induced by PGE2 were not significantly altered. 7 The hypotension induced by prostacyclin is due to two components, a direct relaxation of vascular smooth muscle and a reflex, non-cholinergic vasodilatation. The bradycardia is reflex in nature and is partially mediated by the vagus pathway.

Pharmacology & Therapeutics, 1990

Abstraet--Prostacyclin and endothelium-derived relaxing factor (or nitric oxide) are unstable mediators produced by the vascular endothelium, that are important for local regulation of platelet behavior and blood flow. This review focuses on the basic biochemistry and pharmacology of prostacyclin, its interactions with nitric oxide and nitrovasodilator drugs, and the implications of disturbances in this system for vascular disease, particularly hypertension and atherosclerosis. Prostacyclin and its stable analogs are also finding limited therapeutic applications in preservation of platelet function, pulmonary hypertension, and investigation into the cytoprotective and antiatherosclerotic properties is continuing.

Journal of Cerebral Blood Flow & Metabolism, 1984

The effect of haemorrhagic hypotension on the levels of prostaglandin Ez (POEz), thromboxane Bz (TXBz)' and 6-keto prostaglandin Fla (6-keto-POFla) in cortical tissue of rats was studied. Lightly anesthetized rats were subjected to steady-state hypotension for 15 min, with a mean arterial blood pressure of 80, 60, and 40 mm Hg, and compared to a control group of normo

Hypertension, 1983

The ability of vessels (rings of arteries and vena cava) to synthesize prostacyclin (PGIJ "in vitro" was analyzed in the initial (6-day) and chronic (6-week) phase of two-kidney, two clip hypertension. Male Wistar CHbb THOM rats were used. Tissues were incubated for two hours in Krebs solution containing l4 C-arachidonk acid as exogenous substrate. Specimens (in benzene-ethanol 4:1 vol/vol) and the unlabeled standard solutions of arachidonic acid, 6-keto PGF, n , PGf^, and PGE 2 , were spotted on silica gel-G plates for thin layer chromatography. Conversion of l4 C-arachidonic acid to stable metabolite 6-keto PGF, a was used as an index of PGI 2 synthesis. Results shown: 1) PGI 2 is the major PG synthesized by the rat artery wall; 2) PGI 2 synthesis was increased 2.4 times iq the initial 6-day period of development of rendvascular hypertension (RH); 3) no changes in PGI 2 production were observed in arteries during the chronic 6-week period of RH; 4) abdominal vena cava has little or no capacity to produce PGI 2. As PGI 2 is a potent vasodilator, higher production by arteries during the 6-day period suggests that prostacyclin could play a modulator role on peripheral resistance during the initial phase of renal hypertension.

Thrombosis Research, 1977

Journal of Cerebral Blood Flow & Metabolism, 1983

The effects of prostacyclin (PGI2) were studied in isolated cat basilar and middle cerebral arteries and in human pial arteries. In feline vessels with low resting tension, PGI2had a contractile effect that reached a maximum of 132% (basilar artery) and 23% (middle cerebral artery) of the potassium-induced (127 m M) contraction. In potassium-contracted feline vessels, PGI2caused a further contraction. When these vessels were contracted by PGF2α, PGI2induced relaxation, which was most marked in the middle cerebral artery. PGI2consistently relaxed the middle cerebral artery contracted by the prostaglandin endoperoxide analogue U-44069, whereas the basilar artery was almost unaffected. In human pial arteries with low resting tension, PGI2had no effects in concentrations below 10−6M, whereas higher concentrations induced contractions. In potassium-contracted (35 or 127 m M) preparations, PGI2in concentrations below 10−6M produced relaxation; in higher concentrations further contraction ...

Prostaglandins, 1978

The blood pressure lowering effects of PGIs in the normal and spontaneously hypertensive rat are described. Comparison of dose response curves for PGIs and PGEs indicate that PGIs is twice as potent as PGEs in the normal rat and 3-4 times more active in the spontaneously hypertensive rat. Furthermore PGIa is equiactive through intracarotid and intrajugular administration indicative of the complete lack of pulmonary inactivation. These findings supported by evidence of enhanced PGIa synthesis in aorta during hypertension support the notion that PGIs could participate in blood pressure control mechanisms.

British Journal of Clinical Pharmacology, 2003

Aims To investigate the acute effects of prostacyclin (FlolanA) on renal haemodynamics, renal tubular function, plasma concentration of angiotensin II (Ang II), aldosterone (Aldo), atrial natriuretic peptide (ANP), arginine vasopressin (AVP), mean arterial blood pressure (MBP), and heart rate (HR). Methods Thirteen healthy control subjects were investigated on two separate occasions in a placebo controlled, randomized, dose-response study of the effect of intravenous infusion of prostacyclin (PGI 2 , FlolanA, 2, 4 and 8 ng kg −1 min −1). Glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured by the use of constant infusion of [ 51 Cr]-EDTA and [ 125 I]-hippurane. Urinary output, urinary sodium excretion, fractional sodium excretion, fractional lithium excretion were measured and hormones were measured using radioimmunoassay. Results During prostacyclin (PGI 2) infusion we observed a significant increase in RPF (PGI 2 : 4.8%; 6.1% and 5.2% vs Plac: −1.5%; −1.9% and −5.8% for 2,4 and 8 ng kg −1 min −1 respectively; P≤0.05 for 4 and 8 ng kg −1 min −1

British Journal of Pharmacology, 1978

The inactivation of prostacyclin (PGI2) in the circulation of anaesthetized dogs has been studied by the blood-bathed organ bioassay technique. 2 Spiral strips of bovine coronary and rabbit coeliac or mesenteric artery detected concentrations of PGI2 of 2 to 5 ng/ml. These tissues were insensitive to concentrations at least 200 fold higher of 15-oxo-PGI2 and 6-oxo-PGF1I. 3 PGI2 assayed on bovine coronary artery, rabbit coeliac artery or rat stomach strip, had a half life in blood of 3.0 + 0.3 min, indicating non-enzymatic degradation. 4 No disappearance could be detected by bovine coronary artery when PGI2 was infused across the lungs (0.1 to 0.5 jig kg-' min-'). However, PGI2 was partially inactivated in passage through vascular beds of hindquarters and liver. 5 Of PGI2 infused into the aorta 35 to 65% escaped inactivation in one complete circulation. Therefore, endogenous PGI2 released from the lungs may function as a circulating hormone.