What does this research mean for the field?

The kallikrein-kinin system regulates blood pressure and its circadian rhythmicity, and exerts protective antihypertrophic and antifibrotic effects in the heart that are mediated by the kinin-B2 receptor. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate the cardiovascular actions of kinins and determine how human tissue kallikrein expression influences blood pressure regulation, circadian rhythmicity, and cardiac remodeling.

August 8, 2000The FASEB Journal

Reduced cardiac hypertrophy and altered blood pressure control in transgenic rats with the human tissue kallikrein gene

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Why the study?

Does the expression of the human tissue kallikrein gene reduce blood pressure and protect against isoproterenol-induced cardiac hypertrophy in rats?

Population

Transgenic rat line harboring the human tissue kallikrein gene, TGR(hKLK1), and control rats

Comparison

Expression of human tissue kallikrein gene (TGR)… vs Control rats

Design

Preclinical

Authors

JSJosé Antônio SilvaSumma Health System RARonaldo C. AraújoUniversidade Federal de São Paulo OBOvidiu Constantin BaltatuCross-Cutting Cardiology

Discussion

Member takes

Implication

Kallikrein-kinin modulation warrants preclinical testing in cardiac disease models; leaves open translation to human hypertension or hypertrophy therapy.

Key Points

To evaluate the cardiovascular actions of kinins and determine how human tissue kallikrein expression influences blood pressure regulation, circadian rhythmicity, and cardiac remodeling.
Generated a transgenic rat line, TGR(hKLK1), expressing the human tissue kallikrein gene under the control of a zinc-inducible metallothionein promoter.
Assessed 24-hour mean arterial pressure, circadian blood pressure and heart rate patterns, and response to dietary zinc supplementation.
Induced cardiac hypertrophy using isoproterenol to evaluate cardiac mass and markers of hypertrophy (atrial natriuretic peptide) and fibrosis (collagen III) with or without the kinin-B2 receptor antagonist icatibant.
Transgenic rats exhibited lower 24-hour mean arterial pressure that decreased further with dietary zinc supplementation, alongside a significantly diminished day/night blood pressure rhythm without alterations in heart rate or locomotor circadian rhythms.
Following isoproterenol administration, transgenic rats showed significantly attenuated increases in cardiac weight and reduced expression of atrial natriuretic peptide and collagen III.
Co-treatment with the kinin-B2 receptor antagonist icatibant completely abolished the cardioprotective, antihypertrophic, and antifibrotic effects in transgenic rats.

Structured PICO

Does the expression of the human tissue kallikrein gene reduce blood pressure and protect against isoproterenol-induced cardiac hypertrophy in rats?

Population

Transgenic rat line harboring the human tissue kallikrein gene, TGR(hKLK1), and control rats

Intervention

Expression of human tissue kallikrein gene (TGR(hKLK1)) under zinc-inducible metallothionein promoter, with or without zinc supplementation; isoproterenol treatment to induce cardiac hypertrophy

Comparator

Control rats

Outcome

24-h mean arterial pressure, day/night rhythm of blood pressure, and cardiac hypertrophy (cardiac weight, ANP, and collagen III expression) after isoproterenol treatmentsurrogate

The kallikrein-kinin system plays an important role in regulating blood pressure and its circadian rhythm, and exerts antihypertrophic and antifibrotic actions in the heart.

Cite This Study

Silva et al. (2000) studied this question.

synapsesocial.com/papers/6a1a0eba05af093a17f6efdc https://doi.org/10.1096/fj.99-1010fje

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Implication

Kallikrein-kinin modulation warrants preclinical testing in cardiac disease models; leaves open translation to human hypertension or hypertrophy therapy.

Reduced cardiac hypertrophy and altered blood pressure control in transgenic rats with the human tissue kallikrein gene

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Reduced cardiac hypertrophy and altered blood pressure control in transgenic rats with the human tissue kallikrein gene

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Also Consider

Also Consider