Sympathetic nervous system and hypertension during prolonged TxA2/PGH2 receptor activation in rats.
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.
Gao
H
H
Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, District of Columbia, USA.
Welch
W J
WJ
DiBona
G F
GF
Wilcox
C S
CS
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002302:Cardiac Output / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D010080:Oxazoles / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000502:physiology*; D017482:Receptors, Thromboxane / Q000502:physiology*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012079:Renal Circulation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D010080:Oxazoles; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D014662:Vasoconstrictor Agents; D018738:Hexamethonium; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C078904:ifetroban; D011224:Prazosin