Rodent models of hypertension

Jama, Hamdi; Muralitharan, Rikeish R.; Xu, Chudan; O’Donnell, Joanne A.; Bertagnolli, Mariane; Broughton, Brad R.S.; Head, Geoffrey A.; Marques, Francine Z.

doi:10.1111/bph.15650

Cited by 42 publications

(37 citation statements)

References 153 publications

(194 reference statements)

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“…Thus, the CB 1 R antagonist AM251 enhanced and the FAAH inhibitor URB597 reduced BP [ 19 ], and URB597 enhanced the fall in BP elicited by AEA [ 46 ]. Similarly, in spontaneously hypertensive (SHR) rats (in which the RAS is overactivated [ 68 ]) but not in their normotensive Wistar Kyoto (WKY) controls, the CB 1 R antagonist rimonabant and the FAAH inhibitor URB597 enhanced and reduced BP, respectively [ 19 ]. The blockade of the hypotensive effect of AEA and WIN55212-2 by AM251 confirms the involvement of CB 1 Rs in the hypotensive action of both compounds [ 46 ].…”

Section: Resultsmentioning

confidence: 99%

Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance

Mińczuk

Baranowska-Kuczko

Krzyżewska

et al. 2022

IJMS

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This review is dedicated to the cross-talk between the (endo)cannabinoid and renin angiotensin systems (RAS). Activation of AT1 receptors (AT1Rs) by angiotensin II (Ang II) can release endocannabinoids that, by acting at cannabinoid CB1 receptors (CB1Rs), modify the response to AT1R stimulation. CB1R blockade may enhance AT1R-mediated responses (mainly vasoconstrictor effects) or reduce them (mainly central nervous system-mediated effects). The final effects depend on whether stimulation of CB1Rs and AT1Rs induces opposite or the same effects. Second, CB1R blockade may diminish AT1R levels. Third, phytocannabinoids modulate angiotensin-converting enzyme-2. Additional studies are required to clarify (1) the existence of a cross-talk between the protective axis of the RAS (Ang II—AT2 receptor system or angiotensin 1-7—Mas receptor system) with components of the endocannabinoid system, (2) the influence of Ang II on constituents of the endocannabinoid system and (3) the (patho)physiological significance of AT1R-CB1R heteromerization. As a therapeutic consequence, CB1R antagonists may influence effects elicited by the activation or blockade of the RAS; phytocannabinoids may be useful as adjuvant therapy against COVID-19; single drugs acting on the (endo)cannabinoid system (cannabidiol) and the RAS (telmisartan) may show pharmacokinetic interactions since they are substrates of the same metabolizing enzyme of the transport mechanism.

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Section: Resultsmentioning

confidence: 99%

Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance

Mińczuk

Baranowska-Kuczko

Krzyżewska

et al. 2022

IJMS

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“…Rats were preferred since rapid metabolism of MCT occurs in mice (Dignam et al, 2022). A dose of 60 mg/kg is sufficiently high to lead to the pathological features of PH (Bonnet et al, 2017;Dignam et al, 2022;Jama et al, 2022). Metformin was administered at 100 mg/kg for 21 days since this protocol had a beneficial effect on PH induced by hypoxia (i.p., 21 days) (Liu et al, 2019) and sugen/hypoxia (orally, 21 days) (Dean et al, 2016) in rats.…”

Section: Methodological Considerationsmentioning

confidence: 99%

Effects of the peripheral CB1 receptor antagonist JD5037 in mono— and polytherapy with the AMPK activator metformin in a monocrotaline-induced rat model of pulmonary hypertension

et al. 2022

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Pulmonary hypertension (PH) is a disease leading to increased pressure in the pulmonary artery and right heart failure. The adenosine monophosphate-activated protein kinase (AMPK) activator, metformin, has a protective effect against PH. CB1 receptor blockade reduces the number of pathological alterations in experimental lung fibrosis. The current study evaluates the effect of the peripheral cannabinoid CB1 receptor antagonist JD5037 in mono- and polytherapy with metformin in rat monocrotaline-induced mild PH. Animals received metformin (100 mg/kg), JD5037 (3 mg/kg), or a combination of both once daily for 21 days. Monocrotaline (60 mg/kg) increased right ventricular (RV) systolic pressure (RVSP), led to RV and lung hypertrophy and remodeling, and decreased oxygen saturation. Metformin partially restored the monocrotaline-induced effects, i.e., decreased RVSP, increased oxygen saturation, and counteracted cardiac fibrotic, hypertrophic, and inflammatory changes. JD5037 modified parameters related to inflammation and/or fibrosis. Only polytherapy with metformin and JD5037 improved Fulton’s index and coronary artery hypertrophy and tended to be more effective than monotherapy against alterations in RVSP, oxygen saturation and coronary artery tunica media vacuolization. In conclusion, monotherapy with JD5037 does not markedly influence the PH-related changes. However, polytherapy with metformin tends to be more efficient than any of these compounds alone.

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“…As a complex, multifactorial and systemic disease that involves multiple organs as systems, an important challenge is the use of an adequate model that emulates all of the components that contribute to the phenotype of essential hypertension. There are genetic and non-genetic models (Jama et al, 2021) but here we will focus on a mouse model of genetic hypertension: the Schlager BPH mice.…”

Section: Genetic Model Of Essential Hypertension: Schlager Bph Micementioning

confidence: 99%

Vascular smooth muscle ion channels in essential hypertension

et al. 2022

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Hypertension is a highly prevalent chronic disease and the major risk factor for cardiovascular diseases, the leading cause of death worldwide. Hypertension is characterized by an increased vascular tone determined by the contractile state of vascular smooth muscle cells that depends on intracellular calcium levels. The interplay of ion channels determine VSMCs membrane potential and thus intracellular calcium that controls the degree of contraction, vascular tone and blood pressure. Changes in ion channels expression and function have been linked to hypertension, but the mechanisms and molecular entities involved are not completely clear. Furthermore, the literature shows discrepancies regarding the contribution of different ion channels to hypertension probably due to differences both in the vascular preparation and in the model of hypertension employed. Animal models are essential to study this multifactorial disease but it is also critical to know their characteristics to interpret properly the results obtained. In this review we summarize previous studies, using the hypertensive mouse (BPH) and its normotensive control (BPN), focused on the identified changes in the expression and function of different families of ion channels. We will focus on L-type voltage-dependent Ca2+ channels (Cav1.2), canonical transient receptor potential channels and four different classes of K+ channels: voltage-activated (Kv), large conductance Ca2+-activated (BK), inward rectifiers (Kir) and ATP-sensitive (KATP) K+ channels. We will describe the role of these channels in hypertension and we will discuss the importance of integrating individual changes in a global context to understand the complex interplay of ion channels in hypertension.

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Rodent models of hypertension

Cited by 42 publications

References 153 publications

Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance

Cross-Talk between the (Endo)Cannabinoid and Renin-Angiotensin Systems: Basic Evidence and Potential Therapeutic Significance

Effects of the peripheral CB1 receptor antagonist JD5037 in mono— and polytherapy with the AMPK activator metformin in a monocrotaline-induced rat model of pulmonary hypertension

Vascular smooth muscle ion channels in essential hypertension

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