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Spinal nicotinic receptor expression in spontaneously hypertensive rats
I M Khan1, K L Youngblood, M P Printz
1Department of Pharmacology, University of California, San Diego, La Jolla 92093, USA.
Hypertension (Dallas, Tex. : 1979)
|December 1, 1996
Summary
Spontaneously hypertensive rats exhibit lower spinal nicotinic receptor numbers than normotensive rats, which hydralazine treatment does not reverse. This suggests altered receptor regulation contributes to hypertension.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Pharmacology
Background:
- Adult spontaneously hypertensive rats (SHR) show exaggerated responses to nicotinic agonists compared to Wistar-Kyoto rats (WKY).
- Paradoxically, adult SHR have lower spinal cord nicotinic receptor numbers than WKY rats.
Purpose of the Study:
- To investigate the relationship between spinal nicotinic receptor expression and hypertension in SHR.
- To determine the effect of antihypertensive treatment on nicotinic receptor numbers in SHR.
Main Methods:
- In vitro ligand binding and in situ autoradiography using epibatidine to measure spinal nicotinic receptor numbers.
- Comparison of receptor numbers in adult and young SHR and WKY rats.
- Assessment of hydralazine treatment effects on blood pressure and receptor numbers in SHR and WKY rats.
Main Results:
- Adult SHR had significantly lower spinal nicotinic receptor numbers than adult WKY and Sprague-Dawley rats.
- Receptor numbers were higher in young (5-week-old) prehypertensive SHR and WKY rats than in adults.
- Hydralazine treatment in SHR reduced blood pressure but did not alter spinal nicotinic receptor numbers.
Conclusions:
- Spinal nicotinic receptor expression is downregulated in adult SHR, independent of blood pressure levels achieved with hydralazine.
- Altered central pressor activity or post-receptor events may downregulate spinal nicotinic receptors in genetically hypertensive rats.