Enhanced Expression of the Endothelin-1 Gene in Blood Vessels of DOCA-Salt Hypertensive Rats: Correlation with Vascular Structure
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Bibliographic record
Abstract
Endothelin (ET)-1 is a potent vasoconstrictor peptide which is also endowed with hypertrophic and mitogenic properties. Enhanced ET-1 gene expression in blood vessels of rats with hypertension induced by deoxycorticosterone acetate (DOCA)-salt has been previously demonstrated. The objective of this study was: (1) to investigate the individual effects of salt and DOCA, and of the development of hypertension in DOCA-salt-hypertensive rats, on ET-1 gene expression in blood vessels; and (2) to correlate the presence of enhanced ET expression and the severity of vascular hypertrophy. By providing salt and/or DOCA to rats which were or were not unilaterally nephrectomized, groups of rats with variable degrees of blood pressure elevation were generated. Increased abundance of ET-1 mRNA and a greater content of immunoreactive ET-1 were found with progression of hypertension in aorta and the mesenteric arterial bed only in unilaterally nephrectomized DOCA-salt-treated rats (DOCA-salt-hypertensive rats). Vascular expression of ET-1 was not enhanced in other DOCA-or salt-treated rats, even when blood pressure rose to a mean systolic pressure of 180 mm Hg. The wet weight of aorta and the mesenteric arterial bed, the media thickness, the media cross-sectional area, and the media-to-lumen ratio of mesenteric small arteries of all groups of rats exhibited a close correlation with systolic blood pressure. In DOCA-salt-hypertensive rats after 5 weeks, in which overexpression of ET-1 was maximal, the vascular morphometric parameters were excessive for the level of systolic blood pressure. However, in DOCA-salt-hypertensive rats treated with the combined ETA/ETBET receptor antagonist bosentan, vascular morphometry correlated closely with blood pressure, even though blood pressure was only slightly lower than than of untreated DOCA-salt-hypertensive rats. These data support the hypothesis that ET-1 gene overexpression in blood vessels may accentuate vascular hypertrophy in some forms of hypertension.
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Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
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