Endotoxin tolerance differentially alters hemodynamic responses to a thromboxane A2 mimetic and phenylephrine
| Autor: | James A. Cook, Perry V. Halushka, K. A. Coffee, G. E. Tempel, Wise Wc |
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| Rok vydání: | 1991 |
| Předmět: |
Agonist
Mean arterial pressure medicine.medical_specialty Thromboxane medicine.drug_class Indomethacin Prostaglandin Blood Pressure Arachidonic Acids Biology chemistry.chemical_compound Thromboxane A2 Phenylephrine Internal medicine medicine Animals Cardiac Output Pharmacology Arachidonic Acid Fatty Acids Hemodynamics Drug Tolerance Prostaglandin Endoperoxides Synthetic Rats Endotoxins Endocrinology chemistry Toxicity lipids (amino acids peptides and proteins) Arachidonic acid Female Vascular Resistance Cardiology and Cardiovascular Medicine Adrenergic alpha-Agonists circulatory and respiratory physiology medicine.drug |
| Zdroj: | Journal of cardiovascular pharmacology. 17(1) |
| ISSN: | 0160-2446 |
| Popis: | Repeated sublethal doses of endotoxin render rats tolerant to lethal doses of endotoxin and reduce thromboxane (Tx) A2 synthesis. Endotoxin-tolerant rats are also more resistant to lethal doses of U46619, a stable TxA2 mimetic. These observations raised the possibility that tolerance may alter hemodynamic responses to TxA2 via one or more mechanisms. Mean arterial pressure (MAP) responses to i.v. injections of the stable TxA2 mimetic U46619 at doses ranging from 0.17 to 8.4 micrograms/kg were determined. Despite an initial lower systemic vascular resistance in tolerant rats compared to control rats (2.4 +/- 0.3 vs 3.1 +/- 0.2 mm Hg/ml/min/100 g of body weight, respectively, p less than 0.05), the maximum pressor response to U46619 was significantly greater (p less than 0.05) at the higher doses of U46619 in tolerant rats compared to control rats. Tolerant and control rats also exhibited qualitatively different changes in MAP in response to U46619. Control rats manifested an initial hypotensive response (15 s) not observed in tolerant rats. In contrast, tolerant rats exhibited no depressor response, but a higher peak pressor response to U46619 than that seen in controls. Since prostaglandins may modulate vascular responses to U46619, subsequent studies were conducted in indomethacin-pretreated or essential fatty acid (EFA) deficient rats that were depleted of arachidonic acid substrate. Either indomethacin or EFA deficiency significantly prevented the initial hypotensive response in control rats, suggesting that prostaglandins may mediate this response to U46619. In additional studies, the MAP response in tolerant and control rats to the alpha 1-adrenergic agonist phenylephrine was determined.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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