Sympathetic Renal Innervation and Resistant Hypertension

Hypertension in chronic renal disease and renovascular disease is often resistant to therapy. Understanding the pathogenic mechanisms responsible for hypertension in these conditions may lead to improved and more targeted therapeutic interventions. Several factors have been implicated in the pathogenesis of hypertension associated with renal disease and/or renal failure. Although the role of sodium retention, total body volume expansion, and hyperactivity of the renin-angiotensin-aldosterone system (RAAS) are well recognized, increasing evidence suggests that afferent impulses from the injured kidney may increase sympathetic nervous system activity in areas of the brain involved in noradrenergic regulation of blood pressure and contribute to the development and maintenance of hypertension associated with kidney disease. Recognition of this important pathogenic factor suggests that antiadrenergic drugs should be an essential component to the management of hypertension in patients with kidney disease, particularly those who are resistant to other modalities of therapy

The Time to Offer Treatments for COVID-19

Introduction: COVID-19 has several overlapping phases. Treatment has focused on the late stage of the disease in hospital. Yet, the continuation of the pandemic is by propagation of the disease in outpatients. The current public health strategy relies solely on vaccines to prevent disease. Areas Covered: We searched the major national registries, pubmed.org, and the preprint servers for all ongoing, completed and published trial results with subject numbers of 100 or more on, and used a targeted search to find announcements of unpublished trial results. As of 2/15/2021, we found 111 publications reporting findings in human studies on 14 classes of agents, and on 9 vaccines. There were 62 randomized controlled studies, the rest retrospective observational analyses. Only 21 publications dealt with outpatient care, the rest all in hospitalized patients. Remdesivir and convalescent plasma have emergency use authorization for hospitalized patients in the U.S.A. There is also support for glucocorticoid treatment of the COVID-19 respiratory distress syndrome. Monoclonal antibodies are authorized for outpatients, but the supply is inadequate to treat all at time of diagnosis. Favipiravir, ivermectin, and interferons are approved in certain countries Expert Opinion: Worldwide vaccination is now underway. Vaccines and antibodies are highly antigen specific and new variants are appearing. There is a need for treatment of outpatients who contract the disease, in addition to mass immunization. We call on public health authorities to authorize treatments with known low risk and potential benefit for use in parallel with mass immunization

Evolving role of calcium antagonists in the management of hypertension

What, if anything, should physicians make of these apparently disparate hazards in a group of drugs that they prescribe so widely? The authors, and many of our colleagues, still believe that most patients clearly benefit from the judicious use of calcium antagonists. Reports of several large, powered prospective, randomized outcome studies including ALLHAT commend the use of long-acting calcium antagonists that, by virtue of their ability to attain more gradual and sustained plasma levels, do not evoke reactive sympathetic activation and consequently are safe. Concomitantly, such formulations should promote increased patient compliance and thereby favorably influence hypertension-related morbidity and mortality

Pleiotropic effects of 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitors on renal function

Pleiotropic, or non-lipid-dependent, effects mediated by 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have important clinical implications for the cardiovascular (CV) system. Atherosclerosis is an inflammatory process accompanied by increases in levels of plasma inflammatory markers and accumulation of immune cells within atherosclerotic plaques. Statins not only decrease serum lipid levels, but also inhibit signaling molecules at several points in inflammatory pathways. The anti-inflammatory effects and improved endothelial function associated with statin therapy are thought to be partly responsible for the reduction in CV morbidity and mortality. In analogy, patients with chronic kidney disease administered statins for CV risk reduction show evidence of improved renal function. However, whether statins confer similar protective benefits on the kidney has not been established. Several lines of evidence suggest that similar etiologic and pathological processes may be involved in CV and chronic kidney diseases. If inflammation and functional changes in the renovascular endothelium contribute to the progression of kidney disease, statins are likely to be effective in the treatment of renal disease. In this review, we critically consider emerging data indicating that statins may modulate renal function by altering the inflammatory response of the kidney and renal vasculature to dyslipidemia. Whether the amelioration of renal function by statins is separable from the lipid-lowering effects of these drugs still remains to be delineated. Other questions that remain to be addressed and issues that should be investigated also are presented

Exercise pressor reflex in humans with end-stage renal disease

Previous work has suggested that end-stage renal disease (ESRD) patients may have an exaggerated sympathetic nervous system (SNS) response during exercise. We hypothesized that ESRD patients have an exaggerated blood pressure (BP) response during moderate static handgrip exercise (SHG 30%) and that the exaggerated BP response is mediated by SNS overactivation, characterized by augmented mechanoreceptor activation and blunted metaboreceptor control, as has been described in other chronic diseases. We measured hemodynamics and muscle sympathetic nerve activity (MSNA) in 13 ESRD and 16 controls during: 1) passive hand movement (PHM; mechanoreceptor isolation); 2) low-level rhythmic handgrip exercise (RHG 20%; central command and mechanoreceptor activation); 3) SHG 30%, followed by posthandgrip circulatory arrest (PHGCA; metaboreceptor activation); and 4) cold pressor test (CPT; nonexercise stimulus). ESRD patients had exaggerated increases in systolic BP during SHG 30%; however, the absolute and relative increase in MSNA was not augmented, excluding SNS overactivation as the cause of the exaggerated BP response. Increase in MSNA was not exaggerated during RHG 20% and PHM, demonstrating that mechanoreceptor activation is not heightened in ESRD. During PHGCA, MSNA remained elevated in controls but decreased rapidly to baseline levels in ESRD, indicative of markedly blunted metaboreceptor control of MSNA. MSNA response to CPT was virtually identical in ESRD and controls, excluding a generalized sympathetic hyporeactivity in ESRD. In conclusion, ESRD patients have an exaggerated increase in SBP during SHG 30% that is not mediated by overactivation of the SNS directed to muscle. SBP responses were also exaggerated during mechanoreceptor activation and metaboreceptor activation, but without concomitant augmentation in MSNA responses. Metaboreceptor control of MSNA was blunted in ESRD, but the overall ability to mount a SNS response was not impaired. Other mechanisms besides SNS overactivation, such as impaired vasodilatation, should be explored to explain the exaggerated exercise pressor reflex in ESRD