Role of afferent and efferent renal nerves in the development of AngII-salt hypertension in rats

Foss, Jason D.; Fiege, Jessica K.; Shimizu, Yoji; Collister, John P.; Mayerhofer, Tim; Wood, Laurel; Osborn, John W.

doi:10.14814/phy2.13602

Cited by 19 publications

(15 citation statements)

References 37 publications

(102 reference statements)

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“…In this context, important is also our finding that RDN significantly decreased BP in sham-operated TGR but not in ACF TGR. This suggests that in TGR, hypertension is associated with increased RSNA, an important finding which contradicts the conclusion from the studies using chronic ANG II infusion [16, 19, 45] that ANG II-dependent hypertension is accompanied by low RSNA and that RDN would not reduce BP in this model. The present findings indicate that this paradigm should be reconsidered.…”

Section: Discussioncontrasting

confidence: 72%

Renal Sympathetic Denervation Attenuates Congestive Heart Failure in Angiotensin II-Dependent Hypertension: Studies with Ren-2 Transgenic Hypertensive Rats with Aortocaval Fistula

Honetschlägerová

Gawryś

Jíchová

et al. 2021

Kidney Blood Press Res

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Objective: We examined if renal denervation (RDN) attenuates the progression of aortocaval fistula (ACF)-induced heart failure or improves renal hemodynamics in Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension. Methods: Bilateral RDN was performed 1 week after creation of ACF. The animals studied were ACF TGR and sham-operated controls, and both groups were subjected to RDN or sham denervation. In separate groups, renal artery blood flow (RBF) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng) 3 weeks after ACF creation. Results: In nondenervated ACF TGR, the final survival rate was 10 versus 50% in RDN rats. RBF was significantly lower in ACF TGR than in sham-operated TGR (6.2 ± 0.3 vs. 9.7 ± 0.5 mL min−1 g−1, p < 0.05), the levels unaffected by RDN. Both doses of ANG II decreased RBF more in ACF TGR than in sham-operated TGR (−19 ± 3 vs. −9 ± 2% and −47 ± 3 vs. −22 ± 2%, p < 0.05 in both cases). RDN did not alter RBF responses to the lower dose, but increased it to the higher dose of ANG II in sham-operated as well as in ACF TGR. NE comparably decreased RBF in ACF TGR and sham-operated TGR, and RDN increased RBF responsiveness. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham-operated TGR (29 ± 3 vs. 17 ± 3%, p < 0.05), the changes unaffected by RDN. ACF creation induced marked bilateral cardiac hypertrophy and lung congestion, both attenuated by RDN. In sham-operated but not in ACF TGR, RDN significantly decreased mean arterial pressure. Conclusion: The results show that RDN significantly improved survival rate in ACF TGR; however, this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.

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Section: Discussioncontrasting

confidence: 72%

Renal Sympathetic Denervation Attenuates Congestive Heart Failure in Angiotensin II-Dependent Hypertension: Studies with Ren-2 Transgenic Hypertensive Rats with Aortocaval Fistula

Honetschlägerová

Gawryś

Jíchová

et al. 2021

Kidney Blood Press Res

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“…However, in this investigation, the absence of renal nerves did not prevent DEX-induced hypertension. These results are consistent with earlier reports where RDNX was not able to eliminate blood pressure elevations in the Dahl NaCl-sensitive rats (Wyss et al, 1987) and salt-sensitive-related hypertension (Foss et al, 2018; Tudorancea et al, 2018). Actually, RDNX exacerbates the response to DEX (Figure 1B); that may be associated with an increase in vascular reactivity.…”

Section: Discussionsupporting

confidence: 93%

Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves

et al. 2019

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Synthetic glucocorticoids (GCs) are widely used to treat inflammatory conditions. However, chronic use of GCs can lead to hypertension. The cause of this undesired side effect remains unclear. Previously, we developed an in vivo rat model to study the mechanisms underlying hypertension induced by the chronic administration of the potent synthetic GC, dexamethasone (DEX) and found that the catecholamine biosynthetic pathway plays an important role. In the current study, we used this model to investigate the role of the adrenal medulla, renal nerves, and other peripheral sympathetic nerves in DEX-induced hypertension. After 5 days of baseline telemetric recording of mean arterial pressure (MAP) and heart rate (HR), rats were subjected to one of the following treatments: renal denervation (RDNX), adrenal medullectomy (ADMX), 6-hydroxydopamine (6-OHDA, 20 mg/kg, i.p.) to induce chemical sympathectomy, or a combination of ADMX and 6-OHDA. On day 11, the animals received vehicle (VEH) or DEX in drinking water for 7 days, with the latter causing an increase in MAP in control animals. ADMX and RDNX by themselves exacerbated the pressor effect of DEX. In the chemical sympathectomy group, DEX still caused a rise in MAP but the response was lower (ΔMAP of 6-OHDA/DEX < VEH/DEX, p = 0.039). However, when ΔMAP was normalized to day 10, 6-OHDA + DEX did not show any difference from VEH + DEX, certainly not an increase as observed in DEX + ADMX or RDNX groups. This indicates that sympathetic nerves do not modulate the pressor effect of DEX. TH mRNA levels increased in the adrenal medulla in both VEH/DEX (p = 0.009) and 6-OHDA/DEX (p = 0.031) groups. In the 6-OHDA group, DEX also increased plasma levels of norepinephrine (NE) (p = 0.016). Our results suggest that the activation of catecholamine synthetic pathway could be involved in the pressor response to DEX in animals even under chemical sympathectomy with 6-OHDA.

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“…For example, RDN in rats did not attenuate HT caused by chronic ANG II infusion or by salt loading and reduced kidney mass. 85,89 In rabbits, RSNA is suppressed in ANG II HT and RDN does not attenuate the HT. 86,87 In dogs, RSNA is not increased in ANG II HT 18,22 and RDN did not substantially ameliorate HT caused by renal artery stenosis 91,92 or by chronic aldosterone infusion.…”

Section: Renal Denervation For Hypertension Therapy Rationale For Rdnmentioning

confidence: 97%

“…Previous studies in experimental animals have shown that RDN has little effect on BP in models of HT with normal/low sympathetic activity such as HT induced by chronic infusion of ANG II or aldosterone, renal artery stenosis, or salt loading in animals with reduced nephron numbers. 62,85,[87][88][89]137 Secondary analyses of data from SYMPLICITY HTN-3 also suggest that RDN may be less effective in patients who have volume-dependent forms of HT. 63 In contrast, RDN has been shown to be highly effective in reducing BP in obesity-induced HT which is associated with increased RSNA and may account for 65-75% of the risk for primary HT as well being a major contributor to treatment resistant HT.…”

Section: In Which Patients Is Rdn Most Likely To Effectively Reduce Bp?mentioning

confidence: 99%

Device-Based Neuromodulation for Resistant Hypertension Therapy

Lohmeier

Hall

2019

Circulation Research

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Despite availability of effective drugs for hypertension therapy, significant numbers of hypertensive patients fail to achieve recommended blood pressure (BP) levels while on ≥3 antihypertensive drugs of different classes. These individuals have a high prevalence of adverse cardiovascular events and are defined as having resistant hypertension (RHT) although nonadherence to prescribed antihypertensive medications is common in patients with apparent RHT. Furthermore, apparent and true RHT often display increased sympathetic activity. Based on these findings, technology was developed to treat RHT by suppressing sympathetic activity with electrical stimulation of the carotid baroreflex and catheter-based renal denervation (RDN). Over the last 15 years, experimental and clinical studies have provided better understanding of the physiological mechanisms that account for BP lowering with baroreflex activation (BA) and RDN and, in so doing, have provided insight into which patients in this heterogeneous hypertensive population are most likely to respond favorably to these device-based therapies. Experimental studies have also played a role in modifying device technology after early clinical trials failed to meet key endpoints for safety and efficacy. At the same time, these studies have exposed potential differences between BA and RDN and common challenges that will likely impact antihypertensive treatment and clinical outcomes in patients with RHT. In this review, we emphasize physiological studies that provide mechanistic insights into BP lowering with BA and RDN in the context of progression of clinical studies, which are now at a critical point in determining their fate in RHT management.

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Role of afferent and efferent renal nerves in the development of AngII-salt hypertension in rats

Cited by 19 publications

References 37 publications

Renal Sympathetic Denervation Attenuates Congestive Heart Failure in Angiotensin II-Dependent Hypertension: Studies with Ren-2 Transgenic Hypertensive Rats with Aortocaval Fistula

Renal Sympathetic Denervation Attenuates Congestive Heart Failure in Angiotensin II-Dependent Hypertension: Studies with Ren-2 Transgenic Hypertensive Rats with Aortocaval Fistula

Dexamethasone Causes Hypertension in Rats Even Under Chemical Blockade of Peripheral Sympathetic Nerves

Device-Based Neuromodulation for Resistant Hypertension Therapy

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