An aldosterone-related system in the ventrolateral medulla oblongata of spontaneously hypertensive and Wistar-Kyoto rats.
1. The actions of aldosterone include mediation of vasoconstriction, vascular fibrosis, endothelial dysfunction and sodium retention. These actions can contribute to hypertension. Recent studies implicate an abnormal aldosterone hormonal system in the brain in hypertension. However, the study of central aldosterone actions is still in its infancy, as the exact location and abundance of its components in the brain are uncertain. 2. We aimed to detect components of the aldosterone cascade in the regions of the ventrolateral medulla oblongata (VLM)-containing neurons that regulate blood pressure and to see whether there are quantitative differences in these components between the spontaneously hypertensive rat (SHR) and normotensive Wistar-Kyoto (WKY) rat models. Tissues from four regions of the brainstem, namely, the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively), rostral pressor area and caudal pressor area, were examined. We measured mRNA expression of aldosterone synthase, mineralocorticoid receptor (MR1), 12-lipoxygenase (12-LO), serum- and glucocorticoid- inducible kinase and K-ras in male rats. Gene expression levels were measured using real-time reverse transcription-polymerase chain reaction. 3. We detected all aldosterone components in all regions of the VLM. The K-ras levels were not significantly different in any of the regions. Expression of MR1 mRNA was lower in the RVLM of SHR (n = 5) compared with WKY rats (n = 5; t = 4.590; P = 0.002) and 12-LO mRNA levels were lower in the CVLM in SHR (n = 6) compared with WKY rats (n = 7; P = 0.04). Thus, we have shown for the first time that components of the aldosterone cascade are present in the VLM. Our results suggest that there may be a differential gene expression profile in the brainstem for genetic hypertension.
Kumar
Natasha N
NN
Department of Physiology, School of Medical Sciences, University of Sydney, New South Wales, Australia.
Goodchild
Ann K
AK
Li
Qun
Q
Pilowsky
Paul M
PM
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics; D019405:Cytochrome P-450 CYP11B2 / Q000235:genetics; D020869:Gene Expression Profiling; D017874:Immediate-Early Proteins / Q000235:genetics; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018161:Receptors, Mineralocorticoid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics; D000099184:Serum-Glucocorticoid Regulated Kinases
D000450:Aldosterone; D001092:Arachidonate 12-Lipoxygenase; D019405:Cytochrome P-450 CYP11B2; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D018631:ras Proteins; D000099184:Serum-Glucocorticoid Regulated Kinases