Related Experiment Video
Updated: Jun 18, 2026
Invasive Hemodynamic Characterization of the Portal-hypertensive Syndrome in Cirrhotic Rats
Published on: August 1, 2018
Mouse hepatic portal venoconstrictive response to vasoconstrictors is much weaker than that in rat
Zhan-Sheng Zhao1, Toshishige Shibamoto, Mikihiro Tsutsumi
1Departments of Physiology II, Kanazawa Medical University, Uchinada Ishikawa, Japan.
Abstract:
We previously reported that the portal venous pressure (PPV) response of perfused mouse livers to various vasoactive agents was much weaker than that of other mammals such as rat, rabbit, and guinea pigs. The purpose of this study was to determine the responsiveness of PPV in in vivo BALB/c mouse to intraportal injections of the 3 major vasoconstrictors of angiotensin II, norepinephrine, and endothelin-1 in comparison with that in Sprague-Dawley rats. In anesthetized spontaneously breathing animals, PPV, systemic arterial pressure, and central venous pressure were directly and continuously measured. The above-mentioned vasoconstrictors were injected into the portal vein as a bolus repetitively at the doses ranging 0.01-100 nmol/kg. A dose-dependent increase in systemic arterial pressure in response to each vasoconstrictor was observed similarly in both mice and rats. All vasoconstrictors also caused a dose-dependent increase in PPV in both species, but the peak levels in mouse did not reach higher than 7 mm Hg, whereas it reached as high as 15-24 mm Hg in rats. Immunostaining for alpha-smooth muscle actin revealed that smooth muscles were distributed substantially in portal venules of rat but scarcely in that of mouse. In conclusion, PPV response to various vasoconstrictors was limited in anesthetized BALB/c mice, as compared with the anesthetized Sprague-Dawley rats, presumably due to small amount of vascular smooth muscle in mouse portal venules.
Insights
Portal venous pressure (PPV) responses to vasoconstrictors are limited in mice compared to rats. This difference is likely due to less vascular smooth muscle in mouse portal venules, impacting drug efficacy studies.
Area of Science:
- Physiology
- Pharmacology
- Comparative Medicine
Background:
- Previous studies indicated a weaker portal venous pressure (PPV) response to vasoactive agents in mouse livers compared to other mammals.
- Understanding species-specific vascular responses is crucial for preclinical research and drug development.
Purpose of the Study:
- To compare the in vivo responsiveness of portal venous pressure (PPV) in BALB/c mice and Sprague-Dawley rats to major vasoconstrictors.
- To investigate the underlying anatomical differences contributing to observed variations in PPV response.
Main Methods:
- Direct and continuous measurement of PPV, systemic arterial pressure, and central venous pressure in anesthetized mice and rats.
- Intraportal bolus injections of angiotensin II, norepinephrine, and endothelin-1 at doses ranging from 0.01-100 nmol/kg.
- Immunostaining for alpha-smooth muscle actin to assess vascular smooth muscle distribution in portal venules.
Main Results:
- Both mice and rats showed a dose-dependent increase in systemic arterial pressure in response to vasoconstrictors.
- Vasoconstrictors induced a dose-dependent increase in PPV in both species, but peak levels were significantly lower in mice (≤7 mm Hg) than in rats (15-24 mm Hg).
- Immunostaining revealed substantial smooth muscle in rat portal venules but scarce smooth muscle in mouse portal venules.
Conclusions:
- Anesthetized BALB/c mice exhibit a limited PPV response to intraportal vasoconstrictors compared to anesthetized Sprague-Dawley rats.
- The reduced vascular smooth muscle in mouse portal venules is a likely cause for the diminished PPV response.
- These findings highlight important physiological differences relevant to interpreting drug effects in preclinical models.
