Sympathetic nervous system and hypertension during prolonged TxA2/PGH2 receptor activation in rats.

Abstract

The thromboxane A2 (TxA2)/prostaglandin H2 (PGH2) receptor mimetic U-46619 (0.6 microgram.kg-1.min-1) was infused into conscious rats receiving a high-salt diet. U-46619 increased the mean arterial pressure (MAP) over 13 days by 25 +/- 2 mmHg, whereas the MAP of vehicle-infused controls did not change (-2 +/- 2 mmHg). In subgroups infused with U-46619, cardiac output was unchanged, whereas renal blood flow was reduced (before: 8.5 +/- 0.8; day 4: 5.7 +/- 0.7 ml/min; P < 0.01). Ifetroban (a specific TxA2/PGH2 receptor antagonist) reduced MAP to basal levels in the group receiving U-46619 when infused intravenously (1-100 micrograms/kg) but not intracerebroventricularly (1-100 ng/kg). Hexamethonium (10 mg/kg i.v., a ganglionic blocking agent) and prazosin (0.1 mg/kg, an alpha-adrenergic antagonist) decreased MAP significantly (P < 0.05) more in the experimental group (hexamethonium, U-46619: -55 +/- 3 vs. vehicle: -43 +/- 4 mmHg; and prazosin, U-46619: 28 +/- 3 vs. vehicle: 17 +/- 2 mmHg). In conclusion, hypertension during prolonged infusions of U-46619 into conscious, salt-loaded rats is accompanied by an increase in total and renal vascular resistance and is dependent on peripheral but not central TxA2/PGH2 receptors and on the autonomic and alpha 1-adrenergic peripheral sympathetic nervous systems.

• Authors: H Gao, W J Welch, G F DiBona, C S Wilcox
• Journal: The American journal of physiology (Am J Physiol) Vol. 273 Issue 2 Pt 2 Pg. H734-9 (Aug 1997) ISSN: 0002-9513 [Print] United States
• PMID: 9277490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antihypertensive Agents
• Bridged Bicyclo Compounds, Heterocyclic
• Oxazoles
• Prostaglandin Endoperoxides, Synthetic
• Receptors, Prostaglandin
• Receptors, Thromboxane
• Receptors, Thromboxane A2, Prostaglandin H2
• Vasoconstrictor Agents
• Hexamethonium
• Thromboxane A2
• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• ifetroban
• Prazosin

Topics

• 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
• Animals
• Antihypertensive Agents (pharmacology)
• Blood Pressure (drug effects)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cardiac Output (drug effects)
• Heart Rate (drug effects)
• Hexamethonium (pharmacology)
• Hypertension (physiopathology)
• Male
• Oxazoles (pharmacology)
• Prazosin (pharmacology)
• Prostaglandin Endoperoxides, Synthetic (pharmacology)
• Rats
• Rats, Sprague-Dawley
• Receptors, Prostaglandin (physiology)
• Receptors, Thromboxane (physiology)
• Receptors, Thromboxane A2, Prostaglandin H2
• Renal Circulation (drug effects)
• Sympathetic Nervous System (physiopathology)
• Thromboxane A2 (analogs & derivatives, pharmacology)
• Time Factors
• Vasoconstrictor Agents (pharmacology)