Vascular effects of metformin. Possible mechanisms for its antihypertensive action in the spontaneously hypertensive rat
Abstract
Metformin, an antidiabetic agent, potentiates insulin action and reduces insulin resistance. We examined the antihypertensive effects and vascular effects of metformin in spontaneously hypertensive rats (SHR). Wistar-Kyoto normotensive (WKY) and SHR were injected with metformin (100 mg/kg) or saline subcutaneously twice daily for 4 weeks. Blood pressure was recorded by a tail-cuff plethesmographic method. Metformin treatment significantly attenuated (P < .05) the increase in blood pressure in metformin treated SHR versus untreated control SHR. At the end of the experimental period of 4 weeks, metformin-treated SHR had a mean blood pressure that was 34 mm lower than that of untreated SHR. Metformin treatment had no significant effect on blood pressure in WKY rats. Treatment of SHR aortic smooth muscle (SM) cells with metformin (2 micrograms/mL) for 24 h significantly decreased (P < .05) arginine vasopressin- and thrombin- stimulated increase in [Ca2+]i. However, metformin treatment did not have a significant effect on the basal [Ca+]i. Incubation of SHR aortic SM cells with OH-L-arginine (25 to 100 mumol/L) for 24 h increased nitrite production in a dose dependent manner. Metformin (5 micrograms/mL) treatment of SM cells increased nitrite production at all concentrations of OH-L-arginine; however, differences were significant (P < .05) only at 25 and 50 mumol/L OH-L-arginine. These results suggest that metformin may be decreasing arterial pressure in the SHR, at least in part, by attenuating the agonist-stimulated [Ca2+]i response in SHR vascular smooth muscle cells.
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In ex-vivo preparations of vascular smooth muscle, a direct vasodilating action of metformin has been reported, possibly due to altered calcium handling.
“Also, in ex-vivo preparations of vascular smooth muscle, a direct vasodilating action of metformin has been reported, possibly due to altered calcium handling (35,37,38).”
From Improved Endothelial Function With Metformin in Type 2 Diabetes Mellitus (2001) · cites this paper as [37]
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- Authors
- Bhalla, R.
- Affiliations
- University of Iowa (US)
- Corresponding author
- Bhalla, R
- Venue
- American Journal of Hypertension
- Publisher
- Oxford University Press (OUP)
- Published
- 1996-06
- Volume
- 9
- Issue
- 6
- Pages
- 570-576
- ISSN
- 0895-7061 (ISSN-L)
- OpenAlex
- W1971082858
- Cited by
- 68
- References
- 34
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 1 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 6 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 1.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (14388, 5p50hl044546-05)
- National Heart, Lung, and Blood Institute (HL-14388, HL-44546, P01HL014388)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- metformin, antihypertensive effect, spontaneously hypertensive rats, vascular smooth muscle, intracellular calcium, vasopressin, thrombin, nitric oxide production, nitrite, aortic smooth muscle cells, blood pressure
- MeSH terms
- Animals, Antihypertensive Agents, Blood Pressure, Calcium, Cells, Cultured, Hypertension, Hypoglycemic Agents, Image Processing, Computer-Assisted, Male, Metformin, Muscle, Smooth, Vascular, Nitric Oxide, Rats, Inbred SHR, Rats, Inbred WKY, Vascular Resistance, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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