OBJECTIVE:Recent studies suggest that the clinical course and outcomes of patients with coronavirus disease 2019 (COVID-19) and myasthenia gravis (MG) are highly variable. We performed a systematic review of the relevant literature with a key aim to assess the outcomes of invasive ventilation, mortality, and hospital length of stay (HLoS) for patients presenting with MG and COVID-19. METHODS:We searched the PubMed, Scopus, Web of Science, and MedRxiv databases for original articles that reported patients with MG and COVID-19. We included all clinical studies that reported MG in patients with confirmed COVID-19 cases via RT-PCR tests. We collected data on patient background characteristics, symptoms, time between MG and COVID-19 diagnosis, MG and COVID-19 treatments, HLoS, and mortality at last available follow-up. We reported summary statistics as counts and percentages or mean±SD. When necessary, inverse variance weighting was used to aggregate patient-level data and summary statistics. RESULTS:Nineteen studies with 152 patients (mean age 54.4 ± 12.7 years; 79/152 [52.0%] female) were included. Hypertension (62/141, 44.0%) and diabetes (30/141, 21.3%) were the most common comorbidities. The mean time between the diagnosis of MG and COVID-19 was7.0 ± 6.3 years. Diagnosis of COVID-19 was confirmed in all patients via RT-PCR tests. Fever (40/59, 67.8%) and ptosis (9/55, 16.4%) were the most frequent COVID-19 and MG symptoms, respectively. Azithromycin and ceftriaxone were the most common COVID-19 treatments, while prednisone and intravenous immunoglobulin were the most common MG treatments. Invasive ventilation treatment was required for 25/59 (42.4%) of patients. The mean HLoS was 18.2 ± 9.9 days. The mortality rate was 18/152 (11.8%). CONCLUSION:This report provides an overview of the characteristics, treatment, and outcomes of MG in COVID-19 patients. Although COVID-19 may exaggerate the neurological symptoms and worsens the outcome in MG patients, we did not find enough evidence to support this notion. Further studies with larger numbers of patients with MG and COVID-19 are needed to better assess the clinical outcomes in these patients.

Background Coronavirus disease 2019 (COVID-19) continues to pose a significant threat to public health worldwide. The purpose of this study was to review current evidence obtained from randomized clinical trials on the efficacy of antivirals for COVID-19 treatment. Methods A systematic literature search was performed using PubMed to identify randomized controlled trials published up to September 4, 2021 that examined the efficacy of antivirals for COVID-19 treatment. Studies that were not randomized controlled trials or that did not include treatment of COVID-19 with approved antivirals were excluded. Risk of bias was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) method. Due to study heterogeneity, inferential statistics were not performed and data were expressed as descriptive statistics. Results Of the 2,284 articles retrieved, 31 (12,440 patients) articles were included. Overall, antivirals were more effective when administered early in the disease course. No antiviral treatment demonstrated efficacy at reducing COVID-19 mortality. Sofosbuvir/daclatasvir results suggested clinical improvement, although statistical power was low. Remdesivir exhibited efficacy in reducing time to recovery, but results were inconsistent across trials. Conclusions Although select antivirals have exhibited efficacy to improve clinical outcomes in COVID-19 patients, none demonstrated efficacy in reducing mortality. Larger RCTs are needed to conclusively establish efficacy.

Purpose: The purpose of this review is to compare the effectiveness of different peripheral nerve blocks and general anesthesia (GA) in controlling postoperative pain after arthroscopic rotator cuff repair (ARCR). Methods: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review was conducted for the period of January 1, 2005, to February 16, 2021, by searching the following databases: PubMed, Cochrane, Embase, and Arthroscopyjournal.org. The primary outcomes of interest included 1-hour, 24-hour, and 48-hour pain scores on a numeric rating scale or visual analog scale (VAS). Inclusion criteria were English language studies reporting on adults (>= 18 years) undergoing ARCR with peripheral nerve blockade. To synthesize subjective pain score data at each evaluation time point across studies, we performed random-effects network meta-regression analyses accounting for baseline pain score as a covariate. Results: A total of 14 randomized controlled trials with 851 patients were included in the meta-analysis. Data from six different nerve block interventions, single-shot interscalene brachial plexus nerve block (s-ISB; 37.8% [322/851]), single-shot suprascapular nerve block (s-SSNB; 9.9% [84/851]), continuous ISB (c-ISB; 17.5% [149/851]), continuous SSNB (c-SSNB; 6.9% [59/851] ), s-ISB combined with SSNB (s-ISB+SSNB; 5.8% [49/851]), s-SSNB combined with axillary nerve block (s-SSNB+ANB; 4.8% [41/851]), as well as GA (17.3% [147/851]) were included. Our meta-analysis demonstrated that c-ISB block had a significant reduction in pain score relative to GA at 1-hour postoperation (mean difference [MD]: -1.8; 95% credible interval [CrI] = -3.4, -.08). There were no significant differences in VAS pain scores relative to GA at 24 and 48 hours postoperatively. However, s-ISB+SSNB had a significant reduction in 48-hour pain score compared to s-ISB (MD = -1.07; 95% CrI = -1.92, -.22). Conclusions: It remains unclear which peripheral nerve block strategy is optimal for ARCR. However, peripheral nerve blocks are highly effective at attenuating postoperative ARCR pain and should be more widely considered as an alternative over general anesthesia alone.

Abstract Introduction Schatzker type III fractures of the tibial plateau require elevation of the depressed portions to regain articular congruity. Balloon tibioplasty has been used as an alternative to conventional metal instruments for elevation of the lateral tibial plateau. This study compared functional outcomes following balloon tibioplasty or conventional osteosynthesis techniques in patients with type III fractures of the tibial plateau. Materials and methods A systematic literature search was performed using PubMed, EMBASE, and Cochrane Library to identify studies published through March 29, 2021, pertaining to balloon tibioplasty or conventional osteosynthesis techniques for type III fractures. Non-human studies, opinion or editorial pieces, systematic reviews, case series (< 5 patients), and articles published in a non-English language were excluded. Primary outcomes were Rasmussen clinical score, range of motion, and Knee Society Score (KSS). A Joanna Briggs Institute (JBI) risk of bias assessment was performed for all studies. Results A total of 95 studies were identified, with 10 studies (and 132 total patients) meeting inclusion criteria: 1 study focused on balloon tibioplasty, 8 studies reported outcomes following conventional osteosynthesis, and 1 study compared outcomes of the two techniques. Mean follow-up times varied widely, from 4 to 76.3 months. Where reported, balloon tibioplasty resulted in good to excellent functional outcomes as indicated by Rasmussen clinical scores (mean 28.3 in a case series; mean 28.9 in a randomized controlled trial) and range of motion (≥ 140° in both studies) 1–2 years following surgery. KSS was not reported consistently enough for comparison. Studies ranged from low to high risk of bias according to the JBI assessment. Conclusions Balloon tibioplasty can lead to excellent functional outcomes in patients with depression fractures of the lateral tibial plateau. More research is needed to directly compare outcomes following treatment with balloon tibioplasty or conventional osteosynthesis techniques.

Objectives: To systematically review the clinical literature reporting the use of Lopinavir/ritonavir (LPV/r) for the treatment of patients with Cornonavirus disease 19 (COVID-19) to assess the efficacy of LPV/r for the treatment of COVID-19. Methods: The authors systematically searched PubMed and MedRxiv databases for studies describing treatment of COVID-19 patients using LPV/r compared to other therapies. Articles were excluded if they were case reports, opinion editorials, preclinical studies, single-armed studies, not written in English, not relevant to the topic, or published before May 2020. The included outcomes were viral clearance as measured by reverse-transcription polymerase chain reaction (RT-PCR) negativity and/or improvement on chest computed tomography (CT), mortality, and adverse events. Results: Among 858 total studies, 16 studies met the inclusion criteria and were included in the qualitative review. These studies consisted of 3 randomized control trials, 3 open-label trials, and 10 observational studies. Most of these studies did not report positive clinical outcomes with LPV/r treatment. Conclusion: The systematic review revealed insufficient evidence of effectiveness and clinical benefit of LPV/r in the treatment of COVID-19 patients. Specifically, LPV/r does not appear to improve clinical outcome, mortality, time to RT-PCR negativity, or chest CT clearance in patients with COVID-19.

The purpose of this systematic review and meta-analysis was to examine clinical outcomes associated with convalescent plasma therapy in COVID-19 patients. We performed a literature search on PubMed, medRxiv, Web of Science, and Scopus to identify studies published up to December 10th, 2020 that examined the efficacy of convalescent plasma treatment for COVID-19. The primary endpoints were mortality, clinical improvement, and hospital length of stay. We screened 859 studies that met the search criteria, performed full-text reviews of 56 articles, and identified 15 articles that fulfilled inclusion criteria for meta-analysis. The odds of mortality were significantly lower in the convalescent plasma group compared to the control group (OR = 0.59 [95% CI = 0.44; 0.78], P < .001), although results from two key randomized controlled trials did not support the mortality benefit. The odds of clinical improvement were significantly higher in the convalescent plasma group compared to the control group (OR = 2.02 [95% CI = 1.54; 2.65], P < .001). There was no difference in hospital length of stay between the convalescent plasma group and the control group (MD = -0.49 days [95% CI = -3.11; 2.12], P = .713). In all, these data indicate that a mortality benefit with convalescent plasma is unclear, although there remain benefits with convalescent plasma therapy for COVID-19.

Purpose: To perform a systematic review and meta-analysis of randomized controlled trials that examined remdesivir treatment for COVID-19. Materials and methods: A systematic literature search was performed using Pubmed, Embase, and ClinicalTrials. gov to identify studies published up to October 25, 2020 that examined COVID-19 treatment with remdesivir. A total of 3 randomized controlled trials that consisted of 1691 patients were included in the meta-analysis. Results: The odds for mechanical ventilation (MV) or extracorporeal membrane oxygenation (ECMO) following treatment was significantly lower in the remdesivir group compared to the control group (OR = 0.48 [95% CI: 0.34; 0.69], p < 0.001). The odds of early (at day 14/15; OR = 1.42 [95% CI: 1.16; 1.74], p < 0.001) and late (at day 28/29; OR = 1.44 [95% CI: 1.16; 1.79], p = 0.001) hospital discharge were significantly higher in the remdesivir group compared to the control group. There was no difference in the odds for mortality in patients treated with remdesivir (OR = 0.77 [95% CI: 0.56; 1.06], p = 0.108). Conclusions: Remdesivir attenuates disease progression, leading to lower odds of MV/ECMO and greater odds of hospital discharge for COVID-19 patients. However, remdesivir does not affect odds of mortality.

Maintenance of cerebral blood flow (CBF) is impaired following traumatic brain injury (TBI), increasing the incidence of both ischemic and hemorrhagic events. Vascular tone is controlled by neurogenic, endothelial, and myogenic responses. PURPOSE: This work was designed to specifically determine the extent to which the myogenic response of vascular smooth muscle in the middle cerebral artery (MCA) is altered following TBI. METHODS: TBI was induced by controlled cortical impact (CCI) in 2-month-old male Sprague-Dawley rats. Twenty-four hours following injury or sham surgery, pressurized arterial myography was performed on endothelium-denuded MCA to examine the effect of TBI on smooth muscle-specific vasorelaxation using pharmacologic activators of the adenylyl cyclase (AC)-cAMP-PKA/PKG pathway (10-9M to 10-5M, n=6 at each dose). RESULTS: Myogenic tone was attenuated following TBI (25±1.1% vs. 18±1.2%, n=12; p<0.001). The mean change in myogenic tone in response to activators (10-6M) was reduced to 35% (AC), 33% (PKA), and 30% (PKG) in TBI as compared to sham controls. CONCLUSION: Attenuation of smooth muscle myogenic tone and resulting vasorelaxation following TBI may serve as a compensatory mechanism to protect sensitive brain tissue from cerebral ischemia. Future work will be needed to elucidate the role of pathways that could serve as potential targets for therapeutic intervention to reduce damaging vascular events. Supported by The Florida State University Graduate School Dissertation Award Grant.

Traumatic brain injury (TBI) induces acute changes in cerebrovascular function, including alterations to cerebral artery contractility, which ultimately increase the incidence of both ischemic and hemorrhagic events. Cerebrovascular tone is controlled by hormonal, neurogenic, endothelial, and myogenic responses. Progesterone, a steroid hormone, has been evaluated as a potential treatment to improve TBI outcome; however, progesterone has failed to translate to patient benefits in clinical trials, potentially due to its pleiotropic effects on multiple receptors. Progestin & adipoQ receptor 7 (PAQR7) is a plasma membrane progesterone receptor involved in the vasorelaxation of human blood vessels. However, little is known about the smooth muscle‐specific role of PAQR7 in resistance size cerebral arteries following TBI. Here, we examined PAQR7 function in pressurized endothelium‐denuded cerebral resistance size arteries 24 hours following moderately severe TBI (controlled cortical impact). Baseline myogenic tone of middle cerebral arteries (MCA) was attenuated following TBI. PAQR7‐induced vasorelaxation in pressurized MCA from TBI rats was attenuated in a concentration‐dependent manner as compared to sham controls (10−9M‐10−7M). Moreover, pre‐incubation with inhibitors of adenylyl cyclase (AC), PKA, or PKG attenuated PAQR7‐induced vasorelaxation in both groups. In conclusion, smooth muscle‐specific PAQR7 vasodilation involves an AC‐PKA/PKG pathway in cerebral resistance size arteries, and moderately severe TBI attenuates cerebral artery myogenic tone, which reduces overall arterial vasodilatory capacity.Support or Funding InformationSupported by The Florida State University Graduate School Dissertation Award Grant.

INTRODUCTION: Remote ischemic preconditioning (RIPC) involves brief, serial manually-imposed blood flow restriction of the limbs. The alternating periods of occlusion and reperfusion lead to endothelial adaptations, capable of enhancing blood flow and oxygen delivery. An understanding of the cardiovascular, ventilatory, and local metabolic adjustments to RIPC is essential to optimize the technique as a physiological stimulus. PURPOSE: To investigate reactive and sustained changes in cardiac hemodynamics, local muscle oxygen saturation, and ventilation in response to serial RIPC application. METHODS: Ten (M:4, F:6) recreationally aerobically trained college students (22 ± 2 y, 170.4 ± 9.8 cm, 73.6 ± 8.7 kg, 19.8 ± 6.4 % BF, VO2peak: 45.5 ± 5.0 mL·kg ·min at 208 ± 31 W) received 5-min of alternating-leg blood flow occlusion using a blood pressure cuff (220 mmHg) placed on the upper thighs for a total of 40 min in a supine position. Muscle oxygen saturation (SmO2) was measured continuously using a portable NIRS-based sensor placed over the vastus lateralis. Cardiac hemodynamics were measured continuously using impedance cardiography. Continuous ventilatory changes in response to RIPC were measured in a small subset (n=4) using a metabolic cart. RESULTS: Serial occlusion resulted in a more rapid decrease in SmO2 over time (15.13 ± 2.95 vs. 16.67 ± 2.12 %·min ), and a lower heart rate (61 ± 9 vs. 58 ± 7 bpm) and cardiac output (5.1 ± 0.8 vs. 4.9 ± 0.7 L·min) from occlusion 1 to 4. Serial reperfusion resulted in a greater reactive peak SmO2 (86.7 ± 2.4 vs. 88.3 ± 2.8%), and a lower peak heart rate (74 ± 9 vs. 70 ± 10 bpm) and cardiac output (6.6 ± 0.8 vs. 6.2 ± 0.8 L·min) from reperfusion 1 to 4. Ventilatory data suggest a decrease in oxygen consumption from the first to last occlusion (-0.046 ± 0.013 L·min) and from the first to last reperfusion (-0.030 ± 0.009 L·min). CONCLUSIONS: Both the occlusion and reperfusion stimuli appear less physiologically stressful when applied serially, despite a heightened peak SmO2 following reperfusion. The serial reperfusion response indicates vascular modulation and/or lower local metabolic demand, rather than cardiac hemodynamics, may be responsible for enhancement of local muscle oxygen saturation.

Cardiovascular function declines with age, but patterns of vascular aging differ between the sexes across lifespan. In arterial smooth muscle, transient receptor potential canonical 3 (TRPC3) channels participate in the regulation of intracellular calcium and smooth muscle contractility. The effects of aging on TRPC3 function in female arterial smooth muscle is poorly understood. Here, we investigated physiological function of TRPC3 channels in pressurized, endothelium‐denuded middle cerebral arteries from young (~2 months) and old (~ 20 months) female CD (Sprague Dawley) IGS rats. Myogenic tone (60 mmHg) was similar between young and old cerebral resistance size arteries, however membrane depolarization‐induced vasoconstriction (60 mM K + ) was reduced with age. Application of the selective TRPC3 channel inhibitor, Pyr3 (10 μM), elicited vasodilation in both young and old, however Pyr3‐mediated vasodilation was substantially larger in aged females. Application of 1‐oleoyl‐2‐acetyl‐sn‐glycerol (OAG, 50 μM), a diacylglycerol analog, enhanced myogenic tone to a greater degree in old females as compared to young, while administration of Pyr3+OAG resulted in a greater loss in developed tone in old females. In conclusion, physiological function of TRPC3 channels is elevated with age in female arterial smooth muscle, which could be an important compensatory mechanism to maintain myogenic tone in cerebral resistance size arteries. Support or Funding Information Florida State University This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Traumatic brain injury (TBI) induces acute changes in cerebrovascular function, which include alterations to cerebral artery myogenic tone and autoregulation. In arterial smooth muscle cells (myocytes), large‐conductance calcium‐activated potassium (BK) channels play a vital role in modulating plasma membrane potential and myogenic tone. Here, we examined BK channel expression and function in cerebral resistance size arteries one week following moderately‐severe TBI induced by controlled cortical impact with craniotomy. Total BKα (pore‐forming) and β1 (regulatory) subunit expression were reduced one week post‐TBI. Biotinylation of plasma membrane‐bound proteins revealed a compensatory increase of β1 subunits to the plasma membrane following TBI, which normalized single BK channel activation as assessed using patch‐clamp electrophysiology. However, the loss of total BKα subunits resulted in diminished whole cell, transient BK currents. Pressurized cerebral arteries from TBI rats exhibited greater myogenic tone at 60 mmHg and a diminished response to iberiotoxin, a BK channel pore blocker. In conclusion, moderately‐severe TBI enhances cerebral artery contractility, in part, through reductions in arterial myocyte BK channel subunit expression and function. Moreover, these TBI‐induced alterations in cerebral artery function can persist well beyond the initial 24–48 hour period post‐injury.Support or Funding InformationFlorida State UniversityThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hypertension, a disease that afflicts more than one quarter of the World's population, is a major risk factor for cardiovascular diseases. Blood pressure is determined in part by arterial smooth muscle cells (myocytes) that alter resistance vessel tone. In vivo mechanisms that regulate myocyte contractility to control physiological blood pressure and become pathological during hypertension are poorly understood. Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, although it is unclear if these proteins control physiological blood pressure and can be targeted to alleviate hypertension. Here, we generated the first inducible, smooth muscle‐specific knockout for a TRP channel, namely for PKD2 (TRPP1), to investigate blood pressure regulation by this protein. Data indicate that PKD2 knockout dilates resistance‐size systemic arteries and reduces blood pressure. We show that heterogeneous stimuli activate PKD2 channels in arteries of different organs. Intravascular pressure stimulate PKD2 channels in skeletal muscle arterial myocytes, whereas α1‐adrenergic receptors activate PKD2 channels in myocytes of mesenteric arteries. Regardless of the stimulus or arterial bed, PKD2 current activation in myocytes leads to vasoconstriction. Hypertension is associated with an increase in the abundance of plasma membrane PKD2 channels in systemic arteries. Myocyte‐specific PKD2 knockout caused vasodilation, lowered systemic blood pressure and prevented arterial remodeling during hypertension. In summary, we show that PKD2 channels are activated by distinct vasoconstrictor stimuli in arterial myocytes of different tissues, control physiological systemic blood pressure, are upregulated during hypertension and knockout reduces high blood pressure. These data suggest that targeting of arterial myocyte PKD2 channels could be exploited to control blood pressure and alleviate cardiovascular diseases.Support or Funding InformationThis study was supported by NIH/NHLBI grants HL67061, 133256 and HL137745 to J.H.J, and American Heart Association Scientist Development Grants to S.B and M.D.L.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Systemic blood pressure is determined, in part, by arterial smooth muscle cells (myocytes). Several Transient Receptor Potential (TRP) channels are proposed to be expressed in arterial myocytes, but it is unclear if these proteins control physiological blood pressure and contribute to hypertension in vivo. We generated the first inducible, smooth muscle-specific knockout mice for a TRP channel, namely for PKD2 (TRPP1), to investigate arterial myocyte and blood pressure regulation by this protein. Using this model, we show that intravascular pressure and α1-adrenoceptors activate PKD2 channels in arterial myocytes of different systemic organs. PKD2 channel activation in arterial myocytes leads to an inward Na+ current, membrane depolarization and vasoconstriction. Inducible, smooth muscle cell-specific PKD2 knockout lowers both physiological blood pressure and hypertension and prevents pathological arterial remodeling during hypertension. Thus, arterial myocyte PKD2 controls systemic blood pressure and targeting this TRP channel reduces high blood pressure.

The G protein–coupled estrogen receptor (GPER) is a significant modulator of arterial contractility and blood flow. The GPER‐specific activator, G‐1, has been widely used to characterize GPER function in a variety of tissue types. Large conductance, calcium (Ca2+)‐activated K+ (BK) channels are sensitive to 17β‐estradiol (17β‐E2) and estrogenic compounds (e.g., tamoxifen, ICI 182 780) that target estrogen receptors. The purpose of this study was to investigate the effects of G‐1 on BK channel activation and function in cerebral arterial myocytes. Inside‐out and perforated patch clamp were utilized to assess the effects of G‐1 (50 nmol·L−1‐5 μmol·L−1) on BK channel activation and currents in cerebral arterial myocytes. Pressurized artery myography was used to investigate the effects of G‐1 on vasodilatory response and BK channel function of cerebral resistance size arteries. G‐1 reduced BK channel activation in cerebral arterial myocytes through elevations in BK channel mean close times. Depressed BK channel activation following G‐1 application resulted in attenuated physiological BK currents (transient BK currents). G‐1 elicited vasodilation, but reduced BK channel function, in pressurized, endothelium‐denuded cerebral arteries. These data suggest that G‐1 directly suppresses BK channel activation and currents in cerebral arterial myocytes, BK channels being critically important in the regulation of myocyte membrane potential and arterial contractility. Thus, GPER‐mediated vasodilation using G‐1 to activate the receptor may underestimate the physiological function and relevance of GPER in the cardiovascular system.

Aims:Stromal interaction molecule 1 (STIM1) has emerged as an important player in the regulation of growth and proliferation of smooth muscle cells. Therefore, we hypothesized that STIM1 plays a crucial role in the maintenance of vascular integrity. The objective of this study was to evaluate whether reduced expression of STIM1 could modify the structure and function of the vasculature, leading to changes in blood pressure (BP).Methods and results:Smooth muscle-specific STIM1 knockout (sm-STIM1 KO) in mice resulted in arteries with ∼80% reduced STIM1 protein expression as compared with control mice. Mesenteric vessels exposed to increasing transmural pressure revealed attenuated myogenic reactivity and reduced vasoconstrictor response to phenylephrine in sm-STIM1 KO arteries. BP monitored via telemetry in sm-STIM1 KO and matched controls did not reveal differences. However, heart rate was significantly increased in sm-STIM1 KO mice. Consistent with these findings, plasma catecholamine levels were higher in sm-STIM1 KO than in control mice. Increased sympathetic activity in sm-STIM1 KO mice was unmasked by apha1-adrenergic receptor inhibitor (prazosin) and by treatment with the ganglion-blocking agent, hexamethonium. Both treatments resulted in a greater reduction of BP in sm-STIM1 KO mice. Cytoskeleton of cultured smooth muscle cells was studied by immunocytochemistry using specific antibodies. Staining for actin and vinculin revealed significant alterations in the cytoskeletal architecture of cells isolated from sm-STIM1 KO arteries. Finally, although sm-STIM1 KO mice were protected from Ang II-induced hypertension, such treatment resulted in significant fibrosis and a rapid deterioration of cardiac function.Conclusions:STIM1 deletion in smooth muscle results in attenuated myogenic tone and cytoskeletal defects with detrimental effects on the mechanical properties of arterial tissue. Although BP is maintained by elevated circulating catecholamine, this compensatory stimulation has a deleterious long-term effect on the myocardium.