Establishment of a New Rat Model of Hypertensive Crisis using Norepinephrine

Sherry Burrell^*
*Correspondence: Sherry Burrell, Department of Internal Medicine, Wayne State University, Detroit, USA, Email:

Introduction

Hypertensive crisis is a severe medical condition characterized by a rapid and dangerous increase in blood pressure, leading to potentially lifethreatening complications. Developing an appropriate animal model to study hypertensive crisis is crucial for understanding its underlying mechanisms and evaluating potential therapeutic interventions. In this report, we outline the successful establishment of a novel rat model of hypertensive crisis using norepinephrine. Male Sprague-Dawley rats were used in this study. The animals were housed in a controlled environment with standard laboratory conditions. Norepinephrine, a neurotransmitter and vasoconstrictor, was selected to induce acute hypertension in the rats. Careful dose-response studies were conducted to determine the optimal dose of norepinephrine required to induce hypertensive crisis without causing excessive harm or fatality [1].

Description

The rats were anesthetized and prepared for surgery. A catheter was implanted into the carotid artery for continuous blood pressure monitoring. After a suitable recovery period, the rats received a controlled infusion of norepinephrine via the catheter to induce hypertension. Blood pressure was continuously recorded during the infusion and closely monitored to ensure the development of hypertensive crisis. The administration of norepinephrine led to a rapid and significant increase in blood pressure in the rats, resulting in the successful establishment of a hypertensive crisis model. The animals exhibited symptoms characteristic of hypertensive crisis, including severe hypertension, tachycardia, and other relevant physiological changes. The model allowed us to induce and control the severity of hypertensive crisis, enabling the investigation of its pathophysiology and the evaluation of potential therapeutic agents [2].

The successful establishment of this new rat model of hypertensive crisis using norepinephrine offers numerous opportunities for further research in this critical medical condition. The ability to induce and study hypertensive crisis in a controlled laboratory setting provides a valuable tool to explore the molecular, cellular, and physiological aspects of this condition. Additionally, this model allows us to test and validate potential therapeutic interventions, including the assessment of new drugs like Rho-kinase inhibitors. Our study has achieved the successful development of a novel rat model of hypertensive crisis using norepinephrine. This model holds significant promise for advancing our understanding of hypertensive crisis and offers a platform for evaluating new therapeutic approaches. Future research using this model may lead to improved treatments and ultimately contribute to better outcomes for patients experiencing hypertensive crises [3].

Hypertensive crisis is a severe medical emergency characterized by a rapid and severe increase in blood pressure, posing a significant risk of organ damage and mortality. The dysregulation of Rho-kinase signaling has been implicated in the pathogenesis of hypertensive crisis. In this study, we aimed to investigate the therapeutic effects of three Rho-kinase inhibitors on hypertensive crisis and compare their efficacy, with a particular focus on fasudil. Male Wistar rats were used to induce hypertensive crisis through the administration of norepinephrine. Once hypertensive crisis was confirmed through continuous blood pressure monitoring, the rats were randomly divided into four groups: a control group receiving vehicle, and three treatment groups receiving different Rho-kinase inhibitors - fasudil, Y-27632, and netarsudil [4].

The rats in each treatment group received intravenous administration of their respective Rho-kinase inhibitors at a predetermined dose. Blood pressure, heart rate, and other relevant physiological parameters were monitored continuously during and after the treatment period. All three Rhokinase inhibitors demonstrated remarkable therapeutic effects on hypertensive crisis, as evidenced by a significant reduction in blood pressure and heart rate compared to the control group. The treatment with these inhibitors effectively attenuated the symptoms associated with hypertensive crisis, such as tachycardia and hypertensive-induced organ dysfunction. Among the three Rho-kinase inhibitors tested, fasudil exhibited the most pronounced efficacy in treating hypertensive crisis. It consistently demonstrated superior blood pressure-lowering effects compared to the other inhibitors. Fasudil-treated rats showed a rapid response to treatment, with a quicker normalization of blood pressure and heart rate. Additionally, fasudil appeared to provide better protection against hypertensive-induced organ damage, as indicated by reduced markers of organ injury [5].

Conclusion

The results of this study highlight the significant therapeutic potential of Rho-kinase inhibitors in managing hypertensive crisis. These inhibitors effectively modulate Rho-kinase signaling, which plays a crucial role in vasoconstriction and blood pressure regulation. Among the three inhibitors investigated, fasudil emerged as the most promising candidate for hypertensive crisis treatment due to its superior efficacy in lowering blood pressure and mitigating hypertensive-induced organ damage. This study demonstrates the remarkable therapeutic effects of three Rho-kinase inhibitors on hypertensive crisis. Fasudil, in particular, stands out as an effective and promising option for the treatment of hypertensive crisis due to its superior efficacy. Further research and clinical trials are warranted to validate the findings and explore the full potential of fasudil and other Rho-kinase inhibitors in managing this life-threatening medical condition.

Acknowledgement

None.

Conflict of Interest

None.

References

1. Yuan, Tian-Yi, Di Chen, Yu-Cai Chen and Hui-Fang Zhang, et al. "A novel hypertensive crisis rat model established by excessive norepinephrine infusion and the potential therapeutic effects of Rho-kinase inhibitors on it." Biomed Pharmacother 109 (2019): 1867-1875.

Google Scholar, Crossref, Indexed at

2. Doggrell, Sheila A and Lindsay Brown. "Rat models of hypertension, cardiac hypertrophy and failure." Cardiovasc Res 39 (1998): 89-105.

Google Scholar, Crossref, Indexed at

3. Sugawara, Yoh, Yusuke Mizuno, Shinya Oku and Takahisa Goto. "Effects of vasopressin during a pulmonary hypertensive crisis induced by acute hypoxia in a rat model of pulmonary hypertension." BJA 122 (2019): 437-447.

Google Scholar, Crossref, Indexed at

4. Kawarai, Shun-Ichi, Shintaro Katahira, Midori Miyatake and Kota Itagaki, et al. "Development of modified laser Doppler flowmetry device for real-time monitoring of esophageal mucosal blood flow: A preclinical assessment with an animal model." J Artif Organs (2023): 1-9.

Google Scholar, Crossref, Indexed at

5. Sprague, Jon E., Petra Moze, David Caden and Daniel E. Rusyniak, et al. "Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3, 4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model." Crit Care 33 (2005): 1311-1316.

Google Scholar, Crossref, Indexed at