title: Prostaglandin I2 and thromboxane A2 production in relation to alpha 1 and alpha 2-adrenoreceptor activation in the normotensive and hypertensive rat.
abstract: 1. The perfused mesenteric arterial bed (MAB) from normotensive (WKY) and hypertensive (SHR) rats was used as a model to investigate the relationship between alpha 1 and alpha 2-adrenoreceptor activation and prostanoid release. 2. Prostaglandin I2 (PGI2) and small amounts of thromboxane A2 (TXA2) are released from this preparation and can be monitored in the perfusate under basal and stimulated conditions. 3. Noradrenaline (NA) caused a significant increase in the release of PGI2 from the MAB of both WKY and SHR. Both basal and NA-stimulated PGI2 release were lower in the SHR, whereas pressor responses to NA were higher. Noradrenaline caused a very small increase in TXA2 release in the WKY only and the basal release of this prostanoid was again lower in the SHR. 4. Prazosin, an alpha 1-selective antagonist (10(-10), 10(-9), 10(-8) M) was more effective in blocking pressor responses to NA in the SHR than in the WKY, did not affect the NA-induced release of PGI2 in either group and abolished the small increase of TXA2 release in WKY. 5. Rauwolscine, an alpha 2-selective antagonist (10(-8), 10(-7), 10(-6) M) was more effective in reducing pressor responses to NA in the SHR than in the WKY. It abolished, from 10(-7) M upwards, the NA-induced release of PGI2 in the WKY and reduced it in the SHR. The NA-induced release of TXA2 was abolished in WKY. 6. The observed differences in the effects of rauwolscine and prazosin do not correlate with the effects of these antagonists on pressor responses since both reduce the latter but only rauwolscine abolishes the stimulated PGI2 release. 7. These results indicate that in the SHR, the mechanisms mediating the release of PGI2 from the MAB may be similar but not identical to those in the WKY. The observation that an increase in adrenergically induced pressor responses is not followed by an increase in PGI2 release, which is in fact reduced in the SHR, suggests a more complex regulation of this relationship which may have pathophysiological implications.
authors.affiliation: Department of Pharmacology, Medical School, University of Patras, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Pipili
authors.forename: G
authors.initials: G
authors.lastname: Zoumboulis
authors.forename: M E
authors.initials: ME
authors.lastname: Maragoudakis
mesh_terms: D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D011464:Epoprostenol / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D013928:Thromboxane A2 / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine; D013928:Thromboxane A2; D011464:Epoprostenol; D009638:Norepinephrine; D011224:Prazosin