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Defective modulation of noradrenergic neurotransmission by endogenous prostaglandins in aging spontaneously hypertensive rats.
J Pharmacol Exp Ther. 1989 Jul; 250(1):9-21.JP

Abstract

Sympathetic nerve stimulation causes a greater vascular response in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto normotensive rats (WKY), i.e., noradrenergic neurotransmission is enhanced in SHR. Prejunctional and/or postjunctional defects in the regulation of noradrenergic neurotransmission by endogenous prostaglandins could contribute to the increased responsiveness to sympathetic nerve stimulation in SHR. This hypothesis was tested by comparing the effects in SHR vs. WKY of inhibition of cyclooxygenase on vascular responses to periarterial nerve stimulation (PNS), norepinephrine (NE) and angiotensin II (ang II) in the in situ blood perfused rat mesentery. The cyclooxygenase inhibitor, indomethacin, potentiated vascular responses to PNS and NE similarly in 16-week old SHR vs. age-matched WKY. However, in this age group, indomethacin enhanced responses to ang II more in SHR compared with WKY. To determine whether chronic exposure of the vasculature to high blood pressure might alter the physiological significance of prostaglandin-mediated regulation of noradrenergic neurotransmission in vivo, additional studies were conducted in SHR and WKY that were 25 weeks old. In this age group, neither indomethacin nor ibuprofen, an alternative cyclooxygenase inhibitor, significantly potentiated responses to either PNS or NE in SHR, whereas in WKY both indomethacin and ibuprofen potentiated responses to PNS and NE. Also, in these older animals, indomethacin and ibuprofen enhanced responses to ang II equally in SHR vs. WKY. These findings indicate that in aging SHR prostaglandin-mediated regulation of vascular responses to sympathetic nerve stimulation becomes defective. This defect may contribute to the worsening of high blood pressure with age and may be involved in some of the vascular pathology associated with hypertension.

Authors+Show Affiliations

Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee.

Pub Type(s)

Comparative Study
Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2545868

Citation

Jackson, E K.. "Defective Modulation of Noradrenergic Neurotransmission By Endogenous Prostaglandins in Aging Spontaneously Hypertensive Rats." The Journal of Pharmacology and Experimental Therapeutics, vol. 250, no. 1, 1989, pp. 9-21.
Jackson EK. Defective modulation of noradrenergic neurotransmission by endogenous prostaglandins in aging spontaneously hypertensive rats. J Pharmacol Exp Ther. 1989;250(1):9-21.
Jackson, E. K. (1989). Defective modulation of noradrenergic neurotransmission by endogenous prostaglandins in aging spontaneously hypertensive rats. The Journal of Pharmacology and Experimental Therapeutics, 250(1), 9-21.
Jackson EK. Defective Modulation of Noradrenergic Neurotransmission By Endogenous Prostaglandins in Aging Spontaneously Hypertensive Rats. J Pharmacol Exp Ther. 1989;250(1):9-21. PubMed PMID: 2545868.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defective modulation of noradrenergic neurotransmission by endogenous prostaglandins in aging spontaneously hypertensive rats. A1 - Jackson,E K, PY - 1989/7/1/pubmed PY - 1989/7/1/medline PY - 1989/7/1/entrez SP - 9 EP - 21 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 250 IS - 1 N2 - Sympathetic nerve stimulation causes a greater vascular response in spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto normotensive rats (WKY), i.e., noradrenergic neurotransmission is enhanced in SHR. Prejunctional and/or postjunctional defects in the regulation of noradrenergic neurotransmission by endogenous prostaglandins could contribute to the increased responsiveness to sympathetic nerve stimulation in SHR. This hypothesis was tested by comparing the effects in SHR vs. WKY of inhibition of cyclooxygenase on vascular responses to periarterial nerve stimulation (PNS), norepinephrine (NE) and angiotensin II (ang II) in the in situ blood perfused rat mesentery. The cyclooxygenase inhibitor, indomethacin, potentiated vascular responses to PNS and NE similarly in 16-week old SHR vs. age-matched WKY. However, in this age group, indomethacin enhanced responses to ang II more in SHR compared with WKY. To determine whether chronic exposure of the vasculature to high blood pressure might alter the physiological significance of prostaglandin-mediated regulation of noradrenergic neurotransmission in vivo, additional studies were conducted in SHR and WKY that were 25 weeks old. In this age group, neither indomethacin nor ibuprofen, an alternative cyclooxygenase inhibitor, significantly potentiated responses to either PNS or NE in SHR, whereas in WKY both indomethacin and ibuprofen potentiated responses to PNS and NE. Also, in these older animals, indomethacin and ibuprofen enhanced responses to ang II equally in SHR vs. WKY. These findings indicate that in aging SHR prostaglandin-mediated regulation of vascular responses to sympathetic nerve stimulation becomes defective. This defect may contribute to the worsening of high blood pressure with age and may be involved in some of the vascular pathology associated with hypertension. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2545868/Defective_modulation_of_noradrenergic_neurotransmission_by_endogenous_prostaglandins_in_aging_spontaneously_hypertensive_rats_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2545868 DB - PRIME DP - Unbound Medicine ER -