Biomaterial Database

Thromboxane A2 and prostaglandin endoperoxide analogue effects on porcine renal blood flow. 1990

M Cirino, and H Morton, and C MacDonald, and J Hadden, and A W Ford-Hutchinson

Department of Pharmacology, Merck Frosst Centre for Therapeutic Research, Quebec, Canada.

Thromboxane A2 (TxA2) has been implicated as a mediator of renal and cardiovascular diseases. However, the direct effects of TxA2 on the renal system have been difficult to study because of the instability of the agonist. In the present study injection of synthetic TxA2 directly into the renal artery of anesthetized pigs produced dose-related decreases in renal blood flow (RBF) from 101 +/- 11 to 12 +/- 3 ml/min at the highest dose (20 ng/kg). The reductions in RBF were similar to those produced by the stable prostaglandin endoperoxide analogue, U-44069, although TxA2 was three times more potent. Under these conditions there were no effects on either mean (MAP) or pulmonary arterial pressures (PAP), or the heart rate (HR). The maximal effects produced by TxA2 and U-44069 on RBF were reproducible and the response remained unchanged after pretreatment with either heparin or indomethacin. Systemically administered TxA2 (200 ng/kg iv) increased PAP from 20 +/- 1 to 34 +/- 3 mmHg and this effect was associated with modest increases in MAP and HR. Intravenous administration of the thromboxane receptor antagonist, L-655,240, inhibited the reductions in RBF produced by intrarenal TxA2 and U-44069 and attenuated the cardiopulmonary effects of TxA2 administered intravenously. The results demonstrate directly that TxA2 is a potent agent for decreasing RBF through interaction with a thromboxane receptor.

UI	MeSH Term	Description	Entries
D007211	Indoles	Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
D007267	Injections	Introduction of substances into the body using a needle and syringe.	Injectables,Injectable,Injection
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D011450	Prostaglandin Endoperoxides, Synthetic	Synthetic compounds that are analogs of the naturally occurring prostaglandin endoperoxides and that mimic their pharmacologic and physiologic activities. They are usually more stable than the naturally occurring compounds.	Prostaglandin Endoperoxide Analogs,Prostaglandin Endoperoxide Analogues,Synthetic Prostaglandin Endoperoxides,Analogues, Prostaglandin Endoperoxide,Endoperoxide Analogues, Prostaglandin,Endoperoxides, Synthetic Prostaglandin
D012079	Renal Circulation	The circulation of the BLOOD through the vessels of the KIDNEY.	Kidney Circulation,Renal Blood Flow,Circulation, Kidney,Circulation, Renal,Blood Flow, Renal,Flow, Renal Blood
D006439	Hemodynamics	The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.	Hemodynamic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013552	Swine	Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).	Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D013928	Thromboxane A2	An unstable intermediate between the prostaglandin endoperoxides and thromboxane B2. The compound has a bicyclic oxaneoxetane structure. It is a potent inducer of platelet aggregation and causes vasoconstriction. It is the principal component of rabbit aorta contracting substance (RCS).	Rabbit Aorta Contracting Substance,A2, Thromboxane
D013931	Thromboxanes	Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase.	Thromboxane