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Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat
- Source :
- Canadian journal of physiology and pharmacology. 94(4)
- Publication Year :
- 2016
-
Abstract
- Phenylethanolamine N-methyltransferase (PNMT) is the terminal enzyme in the catecholamine biosynthetic pathway responsible for adrenaline biosynthesis. Adrenaline is involved in the sympathetic control of blood pressure; it augments cardiac function by increasing stroke volume and cardiac output. Genetic mapping studies have linked the PNMT gene to hypertension. This study examined the expression of cardiac PNMT and changes in its transcriptional regulators in the spontaneously hypertensive (SHR) and wild type Wistar-Kyoto (WKY) rats. SHR exhibit elevated levels of corticosterone, and lower levels of the cytokine IL-1β, revealing systemic differences between SHR and WKY. PNMT mRNA was significantly increased in all chambers of the heart in the SHR, with the greatest increase in the right atrium. Transcriptional regulators of the PNMT promoter show elevated expression of Egr-1, Sp1, AP-2, and GR mRNA in all chambers of the SHR heart, while protein levels of Sp1, Egr-1, and GR were elevated only in the right atrium. Interestingly, only AP-2 protein-DNA binding was increased, suggesting it may be a key regulator of cardiac PNMT in SHR. This study provides the first insights into the molecular mechanisms involved in the dysregulation of cardiac PNMT in a genetic model of hypertension.
- Subjects :
- 0301 basic medicine
Cardiac function curve
endocrine system
medicine.medical_specialty
Epinephrine
Transcription, Genetic
Physiology
Interleukin-1beta
Gene Expression
Immunoglobulins
Blood Pressure
030204 cardiovascular system & hematology
Biology
Rats, Inbred WKY
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Spontaneously hypertensive rat
Physiology (medical)
Internal medicine
Rats, Inbred SHR
Genetic model
medicine
Animals
cardiovascular diseases
Heart Atria
Promoter Regions, Genetic
Early Growth Response Protein 1
Pharmacology
Regulation of gene expression
Phenylethanolamine N-Methyltransferase
General Medicine
Phenylethanolamine N-methyltransferase
Rats
Phenylethanolamine
030104 developmental biology
Endocrinology
chemistry
Gene Expression Regulation
Hypertension
cardiovascular system
Catecholamine
Corticosterone
medicine.drug
Subjects
Details
- ISSN :
- 12057541
- Volume :
- 94
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Canadian journal of physiology and pharmacology
- Accession number :
- edsair.doi.dedup.....7b2c170172efe53346262204b8af8aa5