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Endogenous Hydrogen Sulfide in Carotid Bodies Correlates with the Initiation of Hypertension in Spontaneously Hypertensive Rats (SHR)
Author(s) -
Lu Yongjun,
Whiteis Carol A,
Chapleau Mark W,
Abboud Francois M
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.897.9
Subject(s) - endocrinology , medicine , sulfurtransferase , hypoxia (environmental) , carotid body , chemoreceptor , cystathionine beta synthase , prehypertension , spontaneously hypertensive rat , enzyme , chemistry , blood pressure , receptor , carotid arteries , oxygen , biochemistry , cysteine , organic chemistry
Hydrogen sulfide (H 2 S) is a new gaseous mediator of carotid chemoreceptor responses to hypoxia. Its production is determined by cystathionine γ lyase (CSE), cystathionine β synthetase (CBS), and 3‐mercaptopyruvate sulfurtransferase (3MST). Since CSE deletion severely impaired mouse carotid body response to hypoxia, we hypothesized that genetic overexpression of the H 2 S enzymes occurs in carotid bodies of SHR and explains their chemoreceptor hypersensitivity that contributes to hypertension. Carotid bodies were removed from anesthetized male SHR (and their normotensive control WKY rats) when they were young and prehypertensive at 4 weeks, when hypertension was established (at 12 weeks), and when hypertension had been long standing (at 38 weeks). The mRNA expression of CSE, CBS and 3MST was over 100 fold higher (p<0.01) in SHR than in WKY at 4 weeks of age. The expression decreased in SHR to levels that were only slightly higher than WKY at 12 and 38 weeks. The enzyme expression in WKY remained relatively low and stable over time. Expressions in brains of SHR and WKY were comparable. The results indicate a marked overexpression of H 2 S in carotid bodies of SHR during the critical prehypertensive stage. We suggest that this important molecular determinant of chemoreceptor hypersensitivity causes an increase in sympathetic nerve activity, and induces the initiation and development of hypertension. (HL14388)