AJP - Regulatory, Integrative and Comparative Physiology, Vol 272, Issue 5 1493-R1500, Copyright © 1997 by American Physiological Society

ARTICLES

Central thromboxane receptors: mRNA expression and mediation of pressor responses

H. Gao, B. Peng, W. J. Welch and C. S. Wilcox
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, District of Columbia 20007, USA.

These studies tested whether activation of central thromboxane (Tx)A2/prostaglandin (PG) H2 receptors raises blood pressure (BP). Messenger RNA for TxA2/PGH2 receptors was detected in normal Sprague-Dawley rat brain and in rat neuronal and astroglial brain cells in culture. The mean arterial blood pressure (MAP) was recorded in conscious rats during graded administration of the TxA2/PGH2 receptor agonist U-46,619 given intracerebroventricularly or intravenously. Because the pressor responses to intracerebroventricular (but not intravenous) U-46,619 were significantly greater in-high-salt compared with low-salt rats, high-salt rats were used for subsequent studies. The rise in MAP with intracerebroventricular administration of U-46,619 was greater than with intravenous administration and was more sustained. A comparison of plasma radioactivity after intracerebroventricular or intravenous injection of [3H]U-46,619 demonstrated that approximately 35% of the drug reached the systemic circulation by 5-15 min after intracerebroventricular administration. Coadministration of a TxA2/PGH2 antagonist, ifetroban, by intravenous or intracerebroventricular routes blocked the pressor responses induced by U-46,619. The half-maximal inhibition for blockade of responses was substantially lower for intracerebroventricular than for intravenous responses (intracerebroventricular: 0.03 +/- 0.01 vs. intravenous: 3.1 +/- 0.6 micrograms/kg; P < 0.001). The intravenous administration of ifetroban (10 micrograms/kg) caused a greater (P < 0.02) inhibition of pressor responses to U-46,619 (1 microgram/kg) given intravenously (81 +/- 3%) compared with U-46,619 given intracerebroventricularly (40 +/- 13%). In conclusion, TxA2/PGH2 receptor mRNA is expressed in neurons, glial, and brain stem of normal rats. The central administration of a TxA2/PGH2 mimetic raises blood pressure by interaction with specific central and peripheral receptors. This response is augmented in rats fed a high-salt compared with a low-salt diet.

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