Losartan-induced attenuation of blood pressure in l-NAME hypertensive rats is associated with reversal of the enhanced expression of Gi?? proteins
Bibliographic record
Abstract
OBJECTIVE: We have previously reported that hearts from N-[omega]-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats exhibited an enhanced expression of Gi proteins. Since, losartan, an AT1 receptor antagonist, has been shown to attenuate the L-NAME-induced increase in blood pressure, we undertook the present studies to evaluate whether losartan-induced decreased blood pressure in this model of hypertension is associated with attenuation of enhanced expression of Gi proteins and adenylyl cyclase signalling. METHODS: L-NAME (70 mg/kg body weight) and losartan (10 mg/kg body weight), alone or in combination, were given orally to Sprague-Dawley rats for 4 weeks. The control rats received only plain tap water. The levels of inhibitory guanine nucleotide regulatory proteins (Gi alpha-2 and Gi alpha-3) and stimulatory (Gs alpha) proteins and Gi alpha mRNA in hearts were determined by immunoblotting and Northern blotting, respectively. Adenylyl cyclase activity was determined by measuring [32P]cAMP formation from [32P]ATP. RESULTS: Systolic blood pressure was enhanced in L-NAME-treated rats compared to control rats (164 +/- 5.2 versus 105 +/- 2 mmHg; n = 30), and was significantly attenuated by losartan treatment (164 +/- 5.2 mmHg versus 120 +/- 2.5 mmHg; n = 30). The expression of Gi alpha-2 and Gi alpha-3 proteins and their mRNA, which was enhanced in L-NAME-treated rats, was reversed by losartan treatment. However, losartan alone did not alter the levels of Gs alpha or Gi alpha proteins. In addition, the stimulatory effects of guanosine 5'-gamma-thiotriphosphate (GTPgammaS), isoproterenol, 5'-N-ethylcarboxamideadenosine (NECA), glucagon, forskolin (FSK) and sodium fluoride (NaF) on adenylyl cyclase, which were diminished in L-NAME-treated rats, were reversed by losartan treatment. Furthermore, the inhibition of forskolin-stimulated enzyme activity by low concentrations of GTPgammaS (receptor-independent Gi functions), which was significantly enhanced in L-NAME-treated rats, was attenuated by losartan treatment. In addition, losartan was able to reverse the attenuated receptor-mediated inhibitions of adenylyl cyclase by oxotremorine and angiotensin II towards control. CONCLUSIONS: These results suggest the implication of AT1 receptors in enhanced expression of Gi alpha proteins and increased blood pressure in L-NAME-induced hypertension.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".