Ang II-induced contraction is impaired in the aortas of renovascular hypertensive animal model.

Abstract: Renin-angiotensin system plays a critical role in blood pressure control, and the abnormal activation of the AT1 receptor contributes to the development of renovascular hypertension. This study aimed to evaluate the underlying cellular signaling for AT1 receptor activation by Ang II and to compare this mechanism between aortas from 2K-1C and 2K rats. Effects of antagonists and inhibitors were investigated on Ang II-induced contractions in denuded or intact-endothelium aortas. The AT1 receptor antagonist abolished Ang II-induced contraction in 2K-1C and 2K rat aortas, while AT2 and Mas receptors antagonists had no effect. Endothelial nitric oxide synthase inhibition increased the maximal effect (Emax) of Ang II in 2K, which was not changed in 2K-1C aortas. It was associated with lower eNOS mRNA levels in 2K-1C. Endothelium removal increased the Emax of Ang II in 2K-1C and mainly in 2K rat aortas. Nox and COX inhibition did not alter Ang II-induced contraction in 2K and 2K-1C rat aortas. However, AT1 expression was higher in 2K-1C compared to 2K rat aortic rings, whereas expression of phosphorylated (active) IP3 receptors was lower in 2K-1C than in 2K rats. These results demonstrate that endothelium removal impairs Ang II-stimulated contraction in the aorta of 2K-1C rats, which is associated with the reduction of IP3 receptor phosphorylation and activation. In addition, eNOS plays a critical role in Ang II-induced contraction in 2K rat aortas. It is possible that the high Ang II plasma levels could desensitize AT1 receptor in 2K-1C rats, leading to impaired IP3 receptors activation.

Interventions for renal artery stenosis: Appraisal of novel physiological insights and procedural techniques to improve clinical outcome.

Randomized clinical trials failed to show additional benefit of renal artery stenting on top of medical therapy. Instead of writing an obituary on renal artery stenting, we try to explain these disappointing results. A transstenotic pressure gradient is needed to reduce renal perfusion and to activate the renin-angiotensin-aldosterone system. In only a minority of patients included in trials, a transstenotic pressure gradient is measured and reported. Like the coronary circulation, integration of physiological lesion assessment will allow to avoid stenting of non-significant lesions and select those patients that are most likely to benefit from renal artery stenting. Renal artery interventions are associated with peri-procedural complications. Contemporary techniques, including radial artery access, no-touch technique to engage the renal ostium and the use of embolic protection devices, will minimize procedural risk. Combining optimal patient selection and meticulous technique might lead to a netto clinical benefit when renal artery stenting is added to optimal medical therapy.

Role of plasmacytoid dendritic cells in vascular dysfunction in mice with renovascular hypertension.

Endothelial dysfunction and inflammation are clinically significant risk factors for cardiovascular diseases in hypertension. Although immune cells play a role in hypertension, the impact of plasmacytoid dendritic cells in established renovascular hypertension-induced cardiovascular complications is not fully understood. We investigated plasmacytoid dendritic cells' contribution to arterial endothelial dysfunction and inflammation in renovascular hypertension. A two-kidney one-clip (2K1C) model for four weeks in both male and female mice was used to induce renovascular hypertension. We treated mice with or without anti-PDCA-1 antibodies for one week to deplete the plasmacytoid dendritic cells. Renovascular hypertension causes cardiac hypertrophy, lung edema, and microvascular endothelial dysfunction associated with inflammation induction in mice. Moreover, renovascular hypertension affects the profile of immune cells, including dendritic cells and macrophages, with variations between male and female mice. Interestingly, the depletion of plasmacytoid dendritic cells significantly reduces blood pressure, cardiac hypertrophy, lung edema, inflammation, and oxidative stress and improves microvascular endothelial function via the endoplasmic reticulum (ER) stress, autophagy, and mTOR-dependent mechanisms. Plasmacytoid dendritic cells significantly contribute to the development of cardiovascular complications in renovascular hypertension by modulating immune cells, inflammation, oxidative stress, and ER stress.

Apelin-13: a novel approach to suppressing renin production in RVHT.

Renovascular hypertension (RVHT) is characterized by renal artery stenosis and overactivated renin-angiotensin system (RAS). Apelin, known for its negative modulation of RAS, has protective effects against cardiovascular diseases. The role and mechanisms of the primary active form of apelin, apelin-13, in RVHT are unclear. In this study, male Sprague-Dawley rats were divided into control, two-kidney one-clip (2K1C) model, and 2K1C with apelin-13 treatment groups. Renin expression was analyzed using immunohistochemistry and molecular techniques. Full-length (pro)renin receptor (fPRR) and soluble PRR (sPRR) levels were assessed via Western blotting, and cAMP levels were measured using ELISA. Plasma renin content, plasma renin activity (PRA), angiotensin II (ANG II), and sPRR levels were determined by ELISA. Human Calu-6 and mouse As4.1 cells were used to investigate renin production mechanisms. The 2K1C model exhibited increased systolic blood pressure, plasma renin content, PRA, sPRR, and ANG II levels, while apelin-13 treatment reduced these elevations. Apelin-13 inhibited cAMP production, renin mRNA expression, protein synthesis, and PRR/sPRR protein expression in renal tissue. In Calu-6 cells, cAMP-induced fPRR and site-1 protease (S1P)-derived sPRR expression, which was blocked by cAMP-responsive element-binding protein (CREB) inhibition. Apelin-13 suppressed cAMP elevation, CREB phosphorylation, fPRR/sPRR protein expression, and renin production. Recombinant sPRR (sPRR-His) stimulated renin production, which was inhibited by the PRR decoy peptide PRO20 and S1P inhibitor PF429242. These findings suggest that apelin-13 inhibits plasma renin expression through the cAMP/PKA/sPRR pathway, providing a potential therapeutic approach for RVHT. Understanding the regulation of renin production is crucial for developing effective treatments.NEW & NOTEWORTHY Our research elucidated that apelin-13 inhibits renin production through the cAMP/PKA/soluble (pro)renin receptor pathway, presenting a promising therapeutic approach for renovascular hypertension (RVHT) by targeting renin expression mechanisms. These findings underscore the potential of apelin-13 as a novel strategy to address RVHT.

Doppler Ultrasound of the Renal Vasculature.

Ultrasound is the first-line imaging modality used in patients with suspected renovascular disease. Common indications include renovascular hypertension and unexplained renal dysfunction. We review the ultrasound imaging findings of various pathologies involving the renal vessels, including the renal arteries (atherosclerotic stenosis, fibromuscular dysplasia, dissection, arteriovenous fistula, and aneurysm) and veins (tumor and bland thrombus as well as vascular compression syndromes). The current role of renal artery stent placement for atherosclerotic stenosis is also discussed.

Double kiss mini-crush technique to treat complex recurrent renal artery in-stent restenosis.

The double-kiss mini-crush (DKMC) technique has been successfully deployed in the past for the treatment of complex coronary lesions even for left main lesions. Our case report consists of a proof-of-principle that the DKMC technique can be successfully translated as well to the field of complex renal artery lesions. Insightful thinking out-of-the "coronary" box in concert with skillful off-label application of coronary stenting procedures may open the gate for unprecedented opportunities for the treatment of difficult-to-tackle in-stent restenosis in the renal circulation.

Endovascular recanalization for pediatric hypertension secondary to total renal artery occlusion.

PURPOSE: To assess the feasibility and efficacy of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH) secondary to total renal artery occlusion (RAO). METHODS: From 2011 to 2021, 13 pediatric patients with RVH confirmed with 14 occluded renal artery lesions were reviewed. The mean age was11.2 years (range 4 to 16). Nine lesions involved main artery occlusion, while five lesions featured branch occlusion. Blood Pressure Ratio (BPR) was defined as the ratio of the actual BP value to the 95th percentile value adjusted for age, gender, and height. RESULTS: PTRA was performed on nine patients (9/13, 69%). Technical success was achieved in five patients (5/9, 56%), with stent placement in two children (2/9, 22%). During the 12-month follow-up, restenosis was identified in two stent-receiving patients at the 12-month follow-up visit (2/9, 22%). Mean systolic BPR decreased from 1.20 ± 0.07 to 0.96 ± 0.06 (p = 0.003), mean diastolic BPR decreased from 1.19 ± 0.07 to 0.95±0.08 (p = 0.005) and the number of required medications decreased from 3.8 ± 0.8 to 2.4 ± 0.9 (p = 0.052) following PTRA. Subsequent to PTRA, the mean GFR of the occluded kidney improved from 19.5 ± 12.3 mL/ min to 36.3 ± 10.8 mL/ min (p = 0.007) and the mean longitudinal dimension of the affected kidneys significantly increased from 8.2 ± 1.5 cm to 9.2 ± 1.7 cm (p = 0.006). CONCLUSIONS: Endovascular treatment is feasible for pediatric RAO, results in acceptable BP control and preserves renal function.

Chronic red laser treatment induces hypotensive effect in two-kidney one-clip model of renovascular hypertension in rat.

To evaluate whether the chronic effect of photobiomodulation therapy (PBM) on systolic arterial pressure (SAP) from two kidneys one clip (2 K-1C) hypertension animal models can cause a hypotensive effect. Serum levels of nitric oxide were also analyzed and the assessment of lipid peroxidation of the thoracic aorta artery. Male Wistar rats were used. Hypertensive animals (2 K-1C) with Systolic arterial pressure (SAP) greater than or equal to 160 mmHg were used. Systolic arterial pressure (SAP) was determined by the tail plethysmography technique. Normotensive (2 K) and hypertensive (2 K-1C) rats were treated to PBM for 4 weeks using a laser whose irradiation parameters were: red wavelength (λ) = 660 nm: operating continuously; 56 s per point (3 points) spot size = 0.0295 cm2; average optical power of 100 mW; energy of 5.6 J per point; irradiance of 3.40 W/cm2; fluency of 190 J/cm2 per point. The application was on the animals tails, at 3 different points simultaneously, in contact with the skin. To assess serum nitrite and nitrate (NOx) levels, blood collection was performed after chronic PBM treatment, 24 h after the last laser application. The evaluation of the lipid peroxidation of the thoracic aorta artery was performed by measuring the concentration of hydroperoxide by the FOX method. Chronic photobiomodulation therapy (PBM) by red laser (660 nm) can induce a hypotensive effect in 64% of 2 K-1C hypertensive animals, which we say responsive animals. There was no difference in serum NO levels 24 h after the last red laser application, between treated and non-treated groups. Aortic rings from 2 K-1C hypertensive animals present a higher lipid peroxidation. The chronic PBM treatment by red laser decreased aortic rings lipid peroxidation in hypertensive responsive groups, compared to control. our results indicate that chronic PBM made by red laser has an important hypotensive effect in renovascular hypertensive models, by a mechanism that involves decrease in oxidative stress from vascular beds.

Hemodynamic analysis of unilateral and bilateral renal artery stenosis based on fluid-structure interaction.

Renal artery stenosis (RAS) hypertension is a common type of secondary hypertension. This paper aimed to explore how unilateral renal artery stenosis (Uni-RAS) and bilateral renal artery stenosis (Bi-RAS) caused renovascular hypertension with the fluid-structure interaction (FSI) method. Based on a real RAS model, 20 ideal models with different stenosis degrees were established by modifying the stenosis segment. The hemodynamic parameters at different degrees of stenosis, mass flow rate (MFR), pressure drop (PD), fractional flow reserve (FFR), oscillatory shear index (OSI), and relative residence time (RRT), were numerically calculated by the computational fluid dynamics (CFD) method. The numerical results showed that RAS caused the decrease of MFR, and the increase of PD and the proportion of high OSI and high RRT. In the case of RAS, it could not be regarded as a reference indicator for causing renovascular hypertension that the value of FFR was greater than 0.9. In addition, the results of the statistical analysis indicated that Uni-RAS and Bi-RAS were statistically different for MFR, PD and the proportion of high RRT.

Unique presentation of renovascular hypertension due to fibromuscular dysplasia.

A 21-year-old female with a history of right nephrectomy due to trauma presented with several years of multidrug-resistant hypertension. Her workup included negative findings from autoimmune and vasculitides panels and urine catecholamine testing. Computed tomography showed an acute hairpin turn of her left renal artery. Intraoperatively, the artery demonstrated kinking with exhalation. She underwent excision of the diseased portion of the renal artery and an end-to-end anastomosis. Final pathologic examination demonstrated fibromuscular dysplasia. This is a unique case of mechanical artery kinking combined with fibromuscular dysplasia contributing to renovascular hypertension, for which open surgery was beneficial at improving the patient's hypertension.

End-Organ Damage in Hypertension: An Insight on a Differentiated Outpatient Consultation.

OBJECTIVE: The objective of this study was to determine the prevalence of end-organ damage in hypertensive patients attending an outpatient consultation. MATERIALS AND METHODS: Patients were selected from an outpatient consultation at a tertiary hospital care center. All patients who consulted between July 2022 and March 2023 were included. Data on demographic characteristics, blood pressure records, hypertension etiology, medication use, and the presence of target organ damage were collected. RESULTS: A total of 73 patients were included in the study, with 34 patients being male (46.6%) and 39 patients being female (53.4%). The mean age of the patients was 49.8 years. Among the cases of hypertension, 14 (19.2%) were classified as secondary arterial hypertension (AH). The most common cause of secondary AH was obstructive sleep apnea (OSA) (42.9%). Approximately 23.2% of patients had documented end-organ damage potentially related to hypertension, with kidney disease being the most frequent (n = 10, 13.7%). The most commonly prescribed pharmacological classes were angiotensin-converting enzyme inhibitors and angiotensin II receptor antagonists (n = 46, 63%). CONCLUSION: Despite numerous studies and trials on arterial hypertension, it remains a significant contributor to morbidity and mortality, necessitating the continued awareness of its long-term implications.

Pediatric Renovascular Hypertension: A Pediatric Interventional Radiologist's Perspective.

Renovascular hypertension (RVH) contributes close to one-fourth of the secondary etiologies of hypertension in children and a delay in diagnosis can result in adverse clinical outcomes. RVH in children is clinically silent with elevations in blood pressure measurements sometimes as its sole manifestation. Only a high index of suspicion by the clinician can prompt its detection. Despite the availability of other imaging modalities like ultrasound, computed tomography, and magnetic resonance imaging, digital subtraction angiography is still considered the gold standard to make a diagnosis of RVH. Angioplasty is considered the treatment of choice in appropriately selected patients. In this article, we shall focus on the various imaging findings, and management of RVH in children, which requires a multidisciplinary approach with a special focus on the role of interventional radiology.

Outcomes of percutaneous transluminal renal angioplasty for pediatric renovascular hypertension: a 12-year retrospective single-center experience.

Background: Renovascular disease underlies 5-10% of all childhood hypertension. We evaluated the long-term outcomes of percutaneous transluminal renal angioplasty (PTRA) for pediatric renovascular hypertension (RVH). Methods: Data from 37 children with RVH who underwent PTRA of 45 lesions at our center from January 2010 to January 2022 were retrospectively evaluated. Postoperative blood pressure (BP), glomerular filtration rate (GFR), affected kidney size, restenosis, and complications were analyzed. Results: Mean age, weight, and height of patients at first PTRA was 11.51±4.57 (range, 3-17) years, 45.37±22.29 (range, 13.40-106.00) kg, and 1.46±0.26 (range, 0.92-1.85) m, respectively. Technical success was achieved in 33 of 37 (89.2%) patients and 40 of 45 (88.9%) lesions, without surgery-related complications. At a median of 7.5 (range, 3-14) months, restenosis occurred in 6 (16.7%) patients and 7 (16.3%) lesions (all ostial and 6 with a length >15 mm), yielding a clinical beneficial rate from first PTRA of 83.3%. At 18- and 20-month follow-up the mean kidney length (29 kidneys) increased from 8.89±1.55 to 9.79±1.51 cm (P<0.001) and mean GFR (34 kidneys) from 32.28±19.22 to 41.24±13.24 mL/min (P<0.001). Conclusions: In this retrospective analysis, PTRA for the treatment of pediatric RVH can achieve satisfactory results. Angioplasty was associated with improved BP control and long-term preservation of renal function, as reflected by an increase in affected kidney size and a higher GFR.

Hipertensión como elemento común de trasplante renal con riñón presor y del síndrome de encefalopatía posterior reversible / Hypertension as a common element of renal transplantation with pressor kidney and posterior reversible encephalopathy syndrome

La hipertensión arterial secundaria supone solo un 5-10% de los casos de hipertensión arterial, de ahí la importancia de su sospecha clínica para el diagnóstico. Una de las causas más frecuentes de hipertensión secundaria es la hipertensión renovascular, que se produce por hipoperfusión renal y activación del sistema renina-angiotensina-aldosterona. Además de que la hipertensión arterial supone uno de los factores de riesgo cardiovasculares más prevalente en la población, su mal control puede producir alteraciones neurológicas agudas como el síndrome de leucoencefalopatía posterior reversible (PRES), en el que es característico la aparición de alteraciones visuales. A continuación, exponemos el caso de un paciente trasplantado renal con hipertensión arterial con empeoramiento secundario a estenosis de la arteria renal y desarrollo de PRES. (AU)

Secondary arterial hypertension accounts for only 5-10% of cases of arterial hypertension, hence the importance of its clinical suspicion for diagnosis. One of the most common causes of secondary hypertension is renovascular hypertension, caused by renal hypoperfusion and activation of the renin-angiotensin-aldosterone system. In addition to arterial hypertension being one of the most prevalent cardiovascular risk factors in the population, its poor control can cause acute neurological disorders such as Posterior Reversible Leukoencephalopathy syndrome (PRES), being characteristic the appearance of visuals alterations. Next, we present the case of a kidney transplant patient with well-controlled arterial hypertension with worsening secondary to renal artery stenosis and development of PRES. (AU)

Comparative Analysis of Hypertensive Tubulopathy in Animal Models of Hypertension and Its Relevance to Human Pathology.

Assessment of hypertensive tubulopathy for more than fifty animal models of hypertension in experimental pathology employs criteria that do not correspond to lesional descriptors for tubular lesions in clinical pathology. We provide a critical appraisal of experimental hypertension with the same approach used to estimate hypertensive renal tubulopathy in humans. Four models with different pathogenesis of hypertension were analyzed-chronic angiotensin (Ang) II-infused and renin-overexpressing (TTRhRen) mice, spontaneously hypertensive (SHR), and Goldblatt two-kidney one-clip (2K1C) rats. Mouse models, SHR, and the nonclipped kidney in 2K1C rats had no regular signs of hypertensive tubulopathy. Histopathology in animals was mild and limited to variations in the volume density of tubular lumen and epithelium, interstitial space, and interstitial collagen. Affected kidneys in animals demonstrated lesion values that are significantly different compared with healthy controls but correspond to mild damage if compared with hypertensive humans. The most substantial human-like hypertensive tubulopathy was detected in the clipped kidney of 2K1C rats. For the first time, our study demonstrated the regular presence of chronic progressive nephropathy (CPN) in relatively young mice and rats with induced hypertension. Because CPN may confound the assessment of rodent models of hypertension, proliferative markers should be used to verify nonhypertensive tubulopathy.

Tumor de células yuxtaglomerulares (reninoma) como causa de hipertensión arterial en la adolescencia. A propósito de un caso / Juxtaglomerular cell tumor (reninoma) as a cause of arterial hypertension in adolescents. A case report

La hipertensión arterial (HTA) grave en pediatría responde fundamentalmente a causas secundarias. Presentamos una paciente adolescente de 14 años con HTA grave, alcalosis metabólica e hipopotasemia, secundaria a un tumor de células yuxtaglomerulares productor de renina, diagnosticado luego de dos años de evolución de HTA.

Severe arterial hypertension (HTN) in pediatrics is mainly due to secondary causes. Here we describe the case of a 14-year-old female adolescent with severe HTN, metabolic alkalosis, and hypokalemia, secondary to a renin-secreting juxtaglomerular cell tumor diagnosed after 2 years of HTN progression.

Targeting the adenosine monophosphate-activated protein kinase signalling pathway by bempedoic acid attenuates Angiotensin II-induced cardiac remodelling in renovascular hypertension in rats.

The crosstalk between the renin-angiotensin system and Adenosine monophosphate-activated protein kinase (AMPK) gained significant interest due to their involvement in the pathogenesis of several cardiovascular diseases. Angiotensin II (Ang II) plays a crucial role in developing cardiac remodelling by inducing energy imbalance, inflammation, oxidative and endoplasmic reticulum stress, and transforming growth factor-ß (TGF-ß)-induced fibrosis. Ang II directly or through extracellular signal-regulated kinase (ERK) activation impairs AMPK signalling with well-known antioxidant, anti-inflammatory, and anti-fibrotic effects. AIM: This study aimed to investigate the role of bempedoic acid, a novel antihyperlipidemic drug, in attenuating hypertension-induced cardiac remodelling in rats by modulating Ang II-induced damage and activating the AMPK signalling pathway. METHOD: Sixty adult male Sprague Dawley rats were randomly allocated into the Sham control group, Hypertensive group, Captopril group (30 mg/kg), and Bempedoic acid group (30 mg/kg). Hypertension was induced by left renal artery ligation in all groups except the Sham control group. Treatment with captopril and bempedoic acid started 14 days post-surgy and lasted two weeks. Finally, Hemodynamic measurements and electrocardiographic examination were done followed by heart tissue samples collection for biochemical, histopathological, and immunohistochemical examinations. KEY FINDINGS: Bempedoic acid preserved the cardiac function and electrocardiogram patterns. It inhibited endoplasmic reticulum stress, exhibited antioxidant activity, and increased endothelial nitric oxide synthase activity. Bempedoic acid interfered with ERK signalling pathways, including nuclear factor-κB and TGF-ß, exerting anti-inflammatory and anti-fibrotic effects. SIGNIFICANCE: These findings indicate the cardioprotective and antihypertrophic activity of bempedoic acid, which are suggested to result from energy-independent AMPK downstream signalling activation.

Nonatherosclerotic Renovascular Hypertension.

Renovascular hypertension (RVH) is a secondary form of high blood pressure resulting from impaired blood flow to the kidneys with subsequent activation of the renin-angiotensin-aldosterone system. Often, this occurs due to abnormally small, narrowed, or blocked blood vessels supplying one or both kidneys (ie: renal artery occlusive disease) and is correctable. Juxtaglomerular cells release renin in response to decreased pressure, which in turn catalyzes the cleavage of circulating angiotensinogen synthesized by the liver to the decapeptide angiotensin I. Angiotensin-converting enzyme then cleaves angiotensin I to form the octapeptide angiotensin II, a potent vasopressor and the primary effector of renin-induced hypertension. The effects of angiotensin II are mediated by signaling downstream of its receptors. Angiotensin receptor type 1 is a G-protein-coupled receptor that activates vasoconstrictor and mitogenic signaling pathways resulting in peripheral arteriolar vasoconstriction and increased renal tubular reabsorption of sodium and water which promotes intravascular volume expansion. Angiotensin II stimulates the adrenal cortical release of aldosterone, which promotes renal tubular sodium reabsorption, resulting in volume expansion. Angiotensin II acts on glial cells and regions of the brain responsible for blood pressure regulation increasing renal sympathetic activation. Angiotensin II simulates the release of vasopressin from the pituitary which stimulates thirst and water reabsorption from the kidney to expand the intravascular volume and cause peripheral vasoconstriction (increased sympathetic tone). All of these mechanisms coalesce to increase arterial pressure by way of arteriolar constriction, enhanced cardiac output, and the retention of sodium and water.

Type I Non-ST Segment Elevation Myocardial Infarction (NSTEMI) Followed by Type II in a Young Patient With Fibromuscular Dysplasia (FMD) Presented With Hypertensive Emergency: A Case Report.

This article presents a case report highlighting the association between fibromuscular dysplasia (FMD) and acute myocardial infarction in a 25-year-old female patient with multiple cardiovascular comorbidities. Initially presenting with a hypertensive emergency, the patient subsequently developed acute coronary syndrome. MRI revealed irregular narrowing of the bilateral renal arteries, consistent with a diagnosis of FMD. Further evaluation through cardiac catheterization confirmed 95% stenosis of the mid-circumflex artery, necessitating percutaneous coronary intervention (PCI). Fibromuscular dysplasia has been frequently reported in conjunction with coronary artery dissection leading to acute coronary syndrome, especially in young females. Here, we describe the case of FMD without any coronary artery dissection. The presence of FMD highlights the need for comprehensive evaluation and management in patients with multiple cardiovascular risk factors. The recognition of FMD as an underlying pathology in acute myocardial infarction is crucial for appropriate intervention strategies. In this particular case, PCI was successfully performed to address the significant stenosis of the mid-circumflex artery. These findings emphasize the importance of considering FMD as a potential contributing factor in young patients presenting with acute coronary syndrome, particularly in the context of renal artery involvement. Increased awareness among healthcare providers regarding the association between FMD and acute myocardial infarction can aid in prompt diagnosis, appropriate management, and improved patient outcomes.

Renal and hypothalamic inflammation in renovascular hypertension: role of afferent renal nerves.

Renal denervation (RDN) is a potential therapy for drug-resistant hypertension. However, whether its effects are mediated by ablation of efferent or afferent renal nerves is not clear. Previous studies have implicated that renal inflammation and the sympathetic nervous system are driven by the activation of afferent and efferent renal nerves. RDN attenuated the renal inflammation and sympathetic activity in some animal models of hypertension. In the 2 kidney,1 clip (2K1C) model of renovascular hypertension, RDN also decreased sympathetic activity; however, mechanisms underlying renal and central inflammation are still unclear. We tested the hypothesis that the mechanisms by which total RDN (TRDN; efferent + afferent) and afferent-specific RDN (ARDN) reduce arterial pressure in 2K1C rats are the same. Male Sprague-Dawley rats were instrumented with telemeters to measure mean arterial pressure (MAP), and after 7 days, a clip was placed on the left renal artery. Rats underwent TRDN, ARDN, or sham surgery of the clipped kidney and MAP was measured for 6 wk. Weekly measurements of water intake (WI), urine output (UO), and urinary copeptin were conducted, and urine was analyzed for cytokines/chemokines. Neurogenic pressor activity (NPA) was assessed at the end of the protocol calculated by the depressor response after intraperitoneal injection of hexamethonium. Rats were euthanized and the hypothalamus and kidneys removed for measurement of cytokine content. MAP, NPA, WI, and urinary copeptin were significantly increased in 2K1C-sham rats, and these responses were abolished by both TRDN and ARDN. 2K1C-sham rats presented with renal and hypothalamic inflammation and these responses were largely mitigated by TRDN and ARDN. We conclude that RDN attenuates 2K1C hypertension primarily by ablation of afferent renal nerves which disrupts bidirectional renal neural-immune pathways.NEW & NOTEWORTHY Hypertension resulting from reduced perfusion of the kidney is dependent on renal sensory nerves, which are linked to inflammation in the kidney and hypothalamus. Afferent renal nerves are required for chronic increases in both water intake and vasopressin release observed following renal artery stenosis. Findings from this study suggest an important role of renal sensory nerves that has previously been underestimated in the pathogenesis of 2K1C hypertension.