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Biomedical subjects

L P Feigen

Publications and source records attributed to L P Feigen.

At least 37 records · Page 2Linked to original sources
PubMed1983

Differential effects of leukotrienes C4, D4 and E4 in the canine renal and mesenteric vascular beds.

Although leukotrienes (LTs) have been studied extensively with regard to their influence in the lung and the heart, little is known about the actions of these agents in other important vascular beds. In this study, effects of close-arterial injections of synthetic LTs C4, D4 and E4 were determined in the renal and superior mesenteric vascular beds of anesthetized dogs. In the mesenteric circulation, 0.01 to 0.3 microgram of LTC4 and LTD4 reduced blood flow 20 to 60%. Effects were rapid in onset and flow returned to base line within 2 to 3 min. LTE4 was less potent in the mesenteric circulation and responses were not clearly dose dependent over the same range. In contrast, renal blood flow increased after injections of 3 and 10 micrograms of LTC4 and LTD4 into the renal artery. LTE4 did not influence renal blood flow significantly at these doses. Inhibition of prostaglandin synthesis did not alter responses to these LTs in either vascular bed, suggesting that endogenous prostaglandin synthesis did not mediate or modulate responses to the LTs. Mesenteric vascular responses to LTC4 and LTD4, but not LTE4, were inhibited by the LT receptor antagonist FPL-55712. Because LTs are released in a variety of immunological and inflammatory reactions, their differential effects may lead to a redistribution of peripheral blood flow in these reactions.

Animals↗
PubMed1981

Actions of prostaglandins in peripheral vascular beds.

The prostaglandins comprise a large family of substances that includes primary prostaglandins (PGE2, F2 alpha, D2) prostacyclin (PGI2), and thromboxanes (TxA2, B2), all of which exhibit some vascular activity. The activity of each prostaglandin may be species- and organ-dependent, and the type of prostaglandin produced in a tissue is often dependent on the presence of terminal enzyme systems in that tissue. This paper describes the effects of certain members of the prostaglandin family on the mesenteric and renal vascular beds of anesthetized dogs. In the kidney, arachidonic acid, PGE2, D2, and I2 all produce vasodilation when studied by bolus injection techniques. PGF2 alpha is relatively inactive. In the mesenteric vascular bed arachidonate, PGE2 and PGI2 are vasodilators whereas PGD2 and PGF2 are vasoconstrictors. The direct actions of thromboxanes A2 and the endoperoxide PGH2 are uncertain because of their very short half-lives in plasma. Infusion of prostaglandins E2 and I2 into the left ventricle produces vasodilation in both the kidney and the gut. In the mesenteric vascular bed, however, vasodilation during PGE2 (but not PGI2) infusion is a transient phenomenon and the blood flow returns to control levels within the first few minutes of infusion. The vascular actions of prostaglandins are therefore complex and are dependent not only on organ and species, but on experimental technique as well.

Animals↗
PubMed1981

Differential effects of ibuprofen and indomethacin in the regional circulation of the dog.

The effects of indomethacin and ibuprofen on aortic blood pressure and regional vascular resistances were studied in pentobarbital-anesthetized dogs. In the mesenteric vascular bed, indomethacin produced severe, acute vasoconstriction when administered by i.v. infusion as well as by i.a. injections. Tachyphylaxis developed rapidly to this response. In contrast. ibuprofen did not alter mesenteric blood flow even when a large (50 mg) i.v. bolus was rapidly injected. The mesenteric vasoconstrictor response to indomethacin was not modified when prostaglandin synthesis was inhibited or in the presence of cyproheptadine. Phentolamine exerted only a minor influence on the mesenteric vascular effect of indomethacin. The effects of indomethacin and ibuprofen on aortic blood pressure and renal blood flow were similar. Both agents increased aortic pressure and decreased renal blood flow a small but significant amount, but these responses occurred slowly and were probably not related to the acute mesenteric vasoconstricting effect or indomethacin. The present study demonstrates that these nonsteroidal anti-inflammatory agents have different effects on the mesenteric vascular bed and the data suggest that the vasoconstricting effects of indomethacin are not related to the inhibition of prostaglandin synthesis in the intestine. The data also suggest that the acute vasoconstriction in the mesenteric circulation produced by indomethacin is not mediated to a significant degree by local release of alpha adrenergic agents or serotonin.

Animals↗
PubMed1980

Cardiopulmonary actions of prostaglandin 6-keto-E1 in the anesthetized dog.

The cardiopulmonary actions of prostaglandin (PG) 6-keto-E1, a newly discovered metabolite of PGI2, were investigated in the intact chest dog. Injections of 6-keto-PGE1 into the superior vena cava in doses of 1-30 microgram caused dose-dependent decreases in pulmonary arterial and systemic arterial pressures. Inasmuch as cardiac output increased and left or right atrial pressure was unchanged, the decreases in pulmonary and systemic vascular resistances. Reductions in systemic arterial pressure and systemic vascular resistance were similar when 6-keto-PGE1 was injected into the superior vena cava or into the left atrium suggesting that this newly discovered substance is not inactivated in transit through the pulmonary vascular bed in the dog. Decreases in pulmonary arterial pressure and pulmonary vascular resistance were enhanced when pulmonary vascular tone was elevated by infusion of a stable prostaglandin endoperoxide analog or 15-methyl-PGF2 alpha. The present results demonstrate that 6-keto-PGE1 has significant vasodilator activity in pulmonary and systemic vascular beds in the dog and since this substance is not inactivated in the lung, it would serve as a circulating hormone in this species.

Alprostadil↗
PubMed1979

Evidence for separate PGD2 and PGF2 alpha receptors in the canine mesenteric vascular bed.

Potential interactions between PGD2 and PGF2 alpha in the mesenteric and renal vascular beds were investigated in the anesthetized dog. Regional blood flows were measured with electromagnetic flow probes. PGD2, PGF2 alpha and Norepinephrine (NE) were injected as a bolus directly into the appropriate artery, and responses to these agents were obtained before, during and after infusion of either PGD2 or PGF2 alpha into the left ventricle. In each case, the infused prostaglandin caused vascular effects of its own. Left ventricular infusion of PGD2 reduced responses to local injections of PGD2 in the intestine, and a similar effect was observed for PGF2 alpha, suggesting significant receptor or receptor-like interactions for each of the prostanoids. However, systemic infusion of prostaglandin F2 alpha (20--100 ng/kg/min) had no effect on renal or mesenteric vascular responses to local injection of prostaglandin D2. Similarly, PGD2 administration (100 ng/kg/min) did not affect responses to PGF2 alpha in the intestine. The present results therefore suggest that these prostaglandins, i.e., D2 and F2 alpha, act through separate receptors in the mesenteric and renal vascular beds. In addition, increased prostaglandin F2 alpha levels produced by infusion of F2 alpha reduced mesenteric but not renal blood flow, suggesting that redistribution of cardiac output might participate in side effects often observed with clinical use of this prostaglandin, such as nausea and abdominal pain.

Animals↗
PubMed1979

Cardiovascular actions of prostacyclin (PGI2) in the cat.

The cardiovascular actions of the newly discovered bicyclic prostaglandin, prostacyclin, or PGI2, were compared with those of PGE1 in the anesthetized cat. PGI2 decreased systemic arterial pressure, increased cardiac output and decreased systemic vascular resistance. The decreases in systemic vascular resistance were similar when PGI2 was injected into the left or right atrium, suggesting that prostacyclin is not inactivated in the feline pulmonary vascular bed. PGE1 also decreased systemic arterial pressure and increased cardiac output; however, left atrial administration of this substance produced greater reductions in systemic vascular resistance than right atrial injections, suggesting that PGE1 is inactivated in the feline lung. PGI2 also caused dose-related decreases in perfusion pressure in the renal, hindquarters and mesenteric vascular beds and had the greatest vasodilator activity in the mesenteric vascular bed. PGE1 decreased perfusion pressure in the 3 regional beds, and the overall dilator effects of PGI2 and PGE1 in the peripheral circulation were quite smiliar. The present data show that PGI2 is a potent peripheral vasodilator in the cat and since this substance is not inactivated in the lung, it could serve as a circulating hormone in this species.

Animals↗
PubMed1978

Prostaglandins: renal vascular responses to bradykinin, histamine, and nitroglycerine.

A study was undertaken to evaluate the effects of inhibitors of prostaglandin (PG) synthesis on renal vascular responses to several renal vasodilators in anesthetized dogs. Indomethacin (IND) and meclofenamate (MEC), two dissimilar cyclooxygenase inhibitors were used. An electromagnetic flow probe was placed on the renal artery and a needle was inserted proximal to the probe. Injections of bradykinin, histamine, nitroglycerine, and arachidonic acid (AA) were given before and after administration of IND or MEC, 2.5 mg/kg body wt. In each experiment, inhibition of PG synthesis was estimated by reduction of vasodilator activity following AA injection. Although renal vascular resistance increased slightly after IND or MEC, elevations of renal blood flow in response to injections of bradykinin and nitroglycerine were not affected by PG synthesis inhibitors, whereas percent responses to histamine were enhanced by IND but not MEC. In addition, the action of 5 mg/kg IND on responses to injections and infusions of bradykinin was evaluated. No decrease in vasodilator activity following the kinin was detected in these studies. These results demonstrate that renal vascular responses to bradykinin, histamine, and nitroglycerine were not dependent on endogenously produced products of cyclooxygenase (e.g., prostaglandins) in the kidney of the anesthetized dog.

Animals↗
PubMed1978

Pulmonary and systemic vasodilator effects of the newly discovered prostaglandin, PGI2.

The effects of the newly discovered bicyclic prostaglandin, prostacyclin (PGI2), on the pulmonary and systemic vascular beds were investigated in the anesthetized dog. PGI2 decreased systemic and pulmonary arterial pressures in a dose-related manner when injected into the vena cava in doses of 1--30 microgram. Since left ventricular end-diastolic, left atrial, and right atrial pressures were unchanged, and since cardiac output was increased or unchanged, pulmonary and systemic vascular resistances were decreased. PGI2 was 10 times more potent than prostaglandins E1 or E2 in decreasing aortic pressure when injected intravenously, and the effects of PGI2 on the systemic vascular bed were similar when injected into the vena cava or the left atrium. These data indicate that inactivation of PGI2 is minimal in the lung. The stable prostacyclin metabolite, 6-keto-PGF1alpha, had little hemodynamic effects, suggesting that responses to PGI2 were not due to formation of this metabolite. PGI2 produced dose-dependent increases in blood flow in the mesenteric and renal vascular beds. These data demonstrate that PGI2 has marked vasodilator activity in the pulmonary and systemic vascular beds and suggest that prostacyclin is the only known metabolite of arachidonic acid that dilates the pulmonary and systemic circulations.

Animals↗
PubMed1977

Effects of 13, 14-dehydroprostacyclin methyl ester on the feline intestinal vascular bed.

The effects of a stable PGI2 analog, 13, 14-dehydro-PGI2 methyl ester and several vasoactive hormones were compared in the feline intestinal vascular bed under conditions of controlled blood flow so that changes in perfusion pressure directly reflect changes in vascular resistance. The PGI2 analog decreased perfusion pressure in a dose-dependent fashion when injected in the range of dose of 0.03-3 microgram and was quite similar to PGE2 whereas isoproterenol was somewhat more potent as a vasodilagor in the feline intestinal vascular bed. The present data show that 13, 14-dehydro-PGI2 methyl ester has potent vasodilator activity in the intestinal vascular bed.

Acetylcholine↗
PubMed1977

Renal vascular effects of endoperoxide analogs, prostaglandins, and arachidonic acid.

Renal vascular responses to analogs of prostaglandin H2(PGH2) were investigated in anesthetized dogs. The analogs were potent renal vasoconstrictors whose actions were not affected either by indomethacin or by alpha-adrenergic or angiotensin antagonists. The constrictor activity of the analogs approximated that of norepinephrine. Responses to PGD2 were also obtained. This prostaglandin, previously thought to be inactive, was found to cause renal vasodilation similar to that caused by PGA2. Responses to the prostaglandin precursor, arachidonic acid, were of two types. In some animals, the response was marked vasodilation, whereas in others transient vasoconstriction preceded the vasodilation. These studies demonstrate that PGH2 analogs are potent renal vasoconstrictors and that PGD2 possesses renal vasodilating properties. In addition, it is suggested that the rapid vasoconstrictor portion of the arachidonate response may represent effects of endogneously produced PGH2.

Animals↗
PubMed1977

Effects of alpha-adrenergic blockade on renal function in hemorrhagic shock.

This study was undertaken to determine whether alpha-adrenergic blockade would reverse the altered kidney function in hemorrhagic shock. Urinary excretion of Na+, K+, and total solute were studied in 10 anesthetized dogs before and after administration of phenoxybenzamine (PBZ) in shock. Five of the 10 dogs were used to evaluate the effect of shock on renal hemodynamics. Another group of five dogs was used as controls. Normovolemic shock caused a reduction in renal blood flow (RBF) from 9.0 +/- 1 to 6.0 +/- 0.6 ml/min per kg, and an increase in renal vascular resistance (RVR) (P less than .05). When compared to the untreated shock animals, phenoxybenzamine caused an 83% increase in RBF and a 53% decrease in RVR. Treatment of control animals with phenoxybenzamine resulted in a 10-fold increase in urinary [Na+], while urinary [K+] remained unchanged. Neither urinary [K+] nor urinary [Na+] was affected significantly by PBZ in the shock group. Although the excretion rate for Na+ was increased severalfold in the untreated shocked animals when compared to controls (14.0 +/- 3 vs. 1.7 microneq/min) the excretion rates for K+ (P less than .05) and total osmotically active substances (P less than .01) diminished. Phenoxybenzamine caused significant increases in the excretion rates for Na+ and K+ in both the control and shocked dogs. The observed changes in excretion rates when PBZ was given most likely reflect drug-induced changes in renal hemodynamics.

Animals↗
PubMed1977

Influence of inhibitors of prostaglandin synthesis on renal vascular resistance and on renal vascular responses to vasopressor and vasodilator agents in the cat.

We determined the effects of indomethacin and meclofenamate, two inhibitors of prostaglandin synthesis, on renal vascular resistance and on renal responses to nerve stimulation, pressor and depressor hormones in the in situ feline kidney under conditions of controlled blood flow. Both inhibitors produced a gradual rise in renal vascular resistance which became maximal 15-20 minutes after administration. The increase in renal resistance after indomethacin was not attenuated during intrarenal infusion of either phentolamine or SQ 20881. Pretreatment with propranolol, in a dose sufficient to inhibit renin secretion, also did not attenuate the increase in renal resistance produced by indomethacin. However, infusion of [Sar1-, Ala8]angiotensin II, an angiotensin II antagonist, did attenuate the indomethacin-induced increase in renal vascular resistance. After indomethacin, the vasoconstrictor response to norepinephrine was enhanced, whereas responses to nerve stimulation and angiotensin were unaffected. Although meclofenamate enhanced renal vascular resistance, its effects on vasoconstrictor responses were inconsistent. After indomethacin, the renal dilator response to bradykinin was enhanced; however, dilator responses to nitroglycerin were unaltered. The present data indicate that the increase in renal vascular resistance after indomethacin does not depend on the adrenergic system but may be dependent on the renin-angiotensin system. The inconsistent effect of the inhibitors of synthesis on renal constrictor responses to nerve stimulation suggests that endogenous prostaglandins do not serve to modulate the effects of the sympathetic nervous system on the feline renal vascular bed. These results also indicate that renal dilator responses to bradykninin are not mediated by prostaglandins in the cat.

Animals↗