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April 1, 2001Journal of Hypertension

Angiotensin II and serotonin potentiate endothelin-1-induced vascular smooth muscle cell proliferation

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Population

Growth-arrested rabbit vascular smooth muscle cells (VSMCs)

Comparison

Incubation with endothelin-1, angiotensin II… vs Control or individual vasoconstrictors

Design

Preclinical

Authors

TWTakuya WatanabeFuji Electric (Japan)RPRajbabu PakalaMedStar Washington Hospital Center TKTakashi KatagiriUniversity of Toyama

Discussion

Member takes

Implication

Suggests synergy may promote vascular remodeling; hypothesis-generating for combined receptor blockade, requiring human validation.

Key Points

To investigate the interactions among the vasoconstrictors endothelin-1 (ET-1), angiotensin II (Ang II), and serotonin (5-HT) in stimulating vascular smooth muscle cell (VSMC) proliferation.
Incubated growth-arrested rabbit VSMCs with varying concentrations of ET-1 alone or in combination with Ang II, 5-HT, or both.
Measured VSMC proliferation via [3H]thymidine incorporation into DNA and direct cell count increases.
Evaluated pathway mechanisms using antagonists for ETA/B (TAK044), ETA (BQ123), ETB (BQ788), AT1 (candesartan), and 5-HT2A (sarpogrelate) receptors.
ET-1, Ang II, and 5-HT individually stimulated DNA synthesis dose-dependently, reaching maximal effects of 259% of control at 0.5 µmol/l, 173% at 1 µmol/l, and 205% at 50 µmol/l, respectively.
Combining vasoconstrictors produced synergistic DNA synthesis: ET-1 (0.1 µmol/l) with Ang II (1 µmol/l) reached 341%, ET-1 (0.01 nmol/l) with 5-HT (5 µmol/l) reached 404%, and all three together reached 566% of control.
Proliferation and synergism were inhibited by ETA antagonists (TAK044, BQ123), AT1 antagonist (candesartan), and 5-HT2A antagonist (sarpogrelate), but not by the ETB antagonist (BQ788).

Structured PICO

Population

Growth-arrested rabbit vascular smooth muscle cells (VSMCs)

Intervention

Incubation with endothelin-1 (ET-1), angiotensin II (Ang II), and serotonin (5-HT), alone or in combination, and with receptor antagonists (TAK044, BQ123, BQ788, candesartan, sarpogrelate)

Comparator

Control (untreated cells) or individual vasoconstrictors

Outcome

Vascular smooth muscle cell proliferation (measured by increases in incorporation of [3H]thymidine into DNA and in cell number)surrogate

Angiotensin II and serotonin synergistically potentiate endothelin-1-induced vascular smooth muscle cell proliferation, which can be inhibited by specific receptor antagonists.

Cite This Study

Watanabe et al. (2001) studied this question.

synapsesocial.com/papers/6a71b6fefe4101aa97e0a88b https://doi.org/10.1097/00004872-200104000-00010

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Angiotensin II and serotonin potentiate endothelin-1-induced vascular smooth muscle cell proliferation

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Angiotensin II and serotonin potentiate endothelin-1-induced vascular smooth muscle cell proliferation

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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