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Vascular aldosterone in genetically hypertensive rats
Y Takeda1, I Miyamori, S Inaba
1Second Department of Internal Medicine, School of Medicine, Kanazawa University, Japan.
Abstract:
We have reported that aldosterone is synthesized and cytochrome P450aldo mRNA exists in the vasculature. To clarify the pathophysiological role of vascular aldosterone in hypertension, we compared aldosterone production in the mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSP) with that in Wistar-Kyoto rats (WKY). The expressions of mRNA of cytochrome P450aldo, mineralocorticoid receptor, and alpha 1, Na,K-ATPase in the mesenteric arteries were compared between the two groups. Aldosterone concentration in the perfusate of the vasculature was measured by radioimmunoassay after purification with high-performance liquid chromatography. Cytochrome P450aldo and mineralocorticoid receptor mRNA levels were quantified by Southern blot analysis of the products of reverse-transcribed polymerase chain reaction. Levels of alpha 1 Na,K-ATPase mRNA were measured by Northern blot analysis. Vascular aldosterone and cytochrome P450aldo mRNA levels of 2-week-old SHRSP were significantly increased compared with those of age-matched WKY. However, vascular aldosterone in 4- and 9-week-old SHRSP did not differ from that in age-matched WKY. Expression levels of mineralocorticoid receptor mRNA in the vasculature of 4- and 9-week-old SHRSP were significantly increased compared with those in age-matched WKY. Concentrations of vascular alpha 1 Na,K-ATPase mRNA of 2-, 4-, and 9-week-old SHRSP also were significantly higher than those in age-matched WKY. These results suggest that vascular aldosterone contributes to the pathophysiology of hypertension in SHRSP in the early stage.
Insights
Vascular aldosterone and its mRNA are elevated in young stroke-prone spontaneously hypertensive rats (SHRSP), suggesting a role in early hypertension development. Mineralocorticoid receptor and Na,K-ATPase mRNA also increase in SHRSP vasculature.
Area of Science:
- Cardiovascular Research
- Endocrinology
- Hypertension Pathophysiology
Background:
- Aldosterone synthesis and cytochrome P450aldo mRNA have been identified in the vasculature.
- The specific role of vascular aldosterone in the development of hypertension requires further elucidation.
Purpose of the Study:
- To investigate the pathophysiological role of vascular aldosterone in hypertension.
- To compare aldosterone production and related gene expression in the mesenteric arteries of stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY).
Main Methods:
- Measurement of vascular aldosterone concentration using radioimmunoassay after HPLC purification.
- Quantification of cytochrome P450aldo and mineralocorticoid receptor mRNA via RT-PCR and Southern blot.
- Analysis of alpha 1 Na,K-ATPase mRNA levels using Northern blot.
Main Results:
- Significantly increased vascular aldosterone and cytochrome P450aldo mRNA in 2-week-old SHRSP compared to WKY.
- Elevated mineralocorticoid receptor mRNA in the vasculature of 4- and 9-week-old SHRSP.
- Consistently higher vascular alpha 1 Na,K-ATPase mRNA levels in SHRSP across all age groups (2, 4, and 9 weeks).
Conclusions:
- Vascular aldosterone appears to contribute to the pathophysiology of hypertension during the early stages in SHRSP.
- Increased expression of mineralocorticoid receptor and alpha 1 Na,K-ATPase mRNA in the vasculature of SHRSP suggests potential mechanisms for vascular dysfunction.