Asirvatham-Jeyaraj, Ninitha and Jones, A. Daniel and Burnett, Robert and Fink, Gregory D. (2019) Brain Prostaglandin D2 Increases Neurogenic Pressor Activity and Mean Arterial Pressure in Angiotensin II-Salt Hypertensive Rats. In: HYPERTENSION, 74 (6). pp. 1499-1506.
Full text not available from this repository.Abstract
This study tested whether brain L-PGDS (lipocalin-type prostaglandin PG] D synthase), through prostanoid signaling, might increase neurogenic pressor activity and thereby cause hypertension. Sprague Dawley rats on high-salt diet received either vehicle or Ang II (angiotensin II) infusion. On day 4, the developmental stage of hypertension, brains from different sets of control and Ang II-treated rats were collected for measuring L-PGDS expression, PGD2 levels, and DP1R (type 1 PGD2 receptor) expression. In a different set of 14-day Ang II-salt-treated rats, mini-osmotic pumps were used to infuse either a nonselective COX (cyclooxygenase) inhibitor ketorolac, L-PGDS inhibitor AT56, or DP1R inhibitor BWA868C to test the role of brain COX-PGD2-DP1R signaling in Ang II-salt hypertension. The acute depressor response to ganglion blockade with hexamethonium was used to quantify neurogenic pressor activity. During the developmental stage of Ang II-salt hypertension, L-PGDS expression was higher in cerebrospinal fluid, and PGD2 levels were increased in the choroid plexus, cerebrospinal fluid, and the cardioregulatory brain region rostral ventrolateral medulla. DP1R expression was decreased in rostral ventrolateral medulla. Both brain COX inhibition with ketorolac and L-PGDS inhibition with AT56 lowered mean arterial pressure by altering neurogenic pressor activity compared with vehicle controls. Blockade of DP1R with BWA868C, however, increased the magnitude of Ang II-salt hypertension and significantly increased neurogenic pressor activity. In summary, we establish that the development of Ang II-salt hypertension requires increased COX- and L-PGDS-derived PGD2 production in the brain, making L-PGDS a possible target for treating neurogenic hypertension.
| Item Type: | Journal Article |
|---|---|
| Publication: | HYPERTENSION |
| Publisher: | LIPPINCOTT WILLIAMS & WILKINS |
| Additional Information: | copy right of this article belong to LIPPINCOTT WILLIAMS & WILKINS |
| Keywords: | angiotensin II; brain; hypertension; prostaglandin D2; rats |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology |
| Date Deposited: | 12 Feb 2020 07:43 |
| Last Modified: | 12 Feb 2020 07:43 |
| URI: | http://eprints.iisc.ac.in/id/eprint/64033 |
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