Home Current Issue Previous Issues Published Ahead-of-Print Collections For Authors Journal Info
Skip Navigation LinksHome > February 2014 - Volume 32 - Issue 2 > Salt, inflammation, pathophysiological mechanisms, and organ...
Text sizing:
Journal of Hypertension:
doi: 10.1097/HJH.0000000000000106
Editor's Corner

Salt, inflammation, pathophysiological mechanisms, and organ damage in hypertension

Zanchetti, Alberto

Free Access
Article Outline
Collapse Box

Author Information

Istituto Auxologico Italiano and Centro Interuniversitario di Fisiologia Clinica e Ipertensione, Università di Milano, Milan, Italy

Correspondence to Professor Alberto Zanchetti, Centro di Fisiologia Clinica e Ipertensione, Università di Milano, Via F. Sforza, 35, 20122 Milan, Italy. Tel: +39 02 50320484; e-mail: alberto.zanchetti@unimi.it/alberto.zanchetti@auxologico.it

The title mentions some of the relevant topics covered by articles in the present issue of the Journal of Hypertension.

Salt is mentioned first because this issue includes an important policy statement of the International Society of Hypertension and the World Hypertension League calling for reducing dietary salt to less than 5 g/day per adult or, at a minimum, reducing salt intake by 30% by 2025, as recommended by the United Nations. The recommendation is addressed to national governments, nongovernmental organizations and, in particular, to the food industry, without the collaboration of which this important goal will be difficult to attain. The Journal of Hypertension is keen to help diffusing this healthy message.

Our Journal has always given keen attention to the role of salt in blood pressure regulation and the pathogenesis of hypertension by publishing original contributions on the topic. Also in this issue, a few articles have investigated the pathophysiological role of salt. By using the large biobank of the Malmö Diet and Cancer Study, Dahlberg et al. (pp. 294–299) have found that the combination of two SNPs in NEDD4L, a regulatory protein of a sodium channel in the distal nephron, that is associated with enhanced salt sensitivity, is also associated with high blood pressure and increased risk of cardiovascular morbidity and mortality. Graham and Padmanabhan, in an editorial commentary (pp. 230–232), extensively review the organization and function of the amiloride-sensitive sodium channel (EnaC), the binding process of NEDD4L to EnaC, and the incremental advance on the role of NEDD4L in essential hypertension provided by the study by Dahlberg et al. Liang et al. (pp. 318–330) report that both swelling-activated Cl currents and Cl channel gene CLC-3 play an independent role in proliferation of pulmonary artery smooth muscle cells, a mechanism leading to pulmonary arterial hypertension. Allen et al. (pp. 374–382) illustrate how dietary salt alters autonomic control of heart rate variability in healthy normotensive young men and women.

The study by Allen et al. relates to other articles dealing with cardiovascular autonomic control. Davern et al. (pp. 352–362) find that Schlager BPH/2J hypertensive rats are resistant to the blood pressure-lowering effects of diazepam, and suggest that GABAA receptor dysfunction in BPH/2J mice may contribute to the neurogenic hypertension by not suppressing arousal induced sympathetic activation within the amygdala and hypothalamic nuclei. Lucini et al. (pp. 363–373), by using autonomic nervous system indices including RR variability and baroreflex gain, have explored the possibility that autonomic proxies may be used clinically to identify hypertensive and normotensive groups. Grassi et al. (pp. 383–388) show that in lean and obese individuals with obstructive sleep apnea (OSA), the adrenergic overdrive is seen in the muscle but not in the cutaneous circulation, and therefore sympathetic activation in OSA is not a generalized phenomenon.

Other articles report studies on OSA and on obesity. In a murine model of sleep apnea, Schulz et al. (pp. 300–305) show that chronic intermittent hypoxia induces hypertension, and the blood pressure increase is mediated by reactive oxygen species derived from an activation of NOX2 within cells located outside the cardiovascular system. In patients with moderate-to-severe OSA, Seif et al. (pp. 267–275) find that increasing levels of the Apnea Hypopnea Index and Oxygen Desaturation Index are associated with increasing odds of nondipping blood pressure. Olszanecka-Glinianowicz et al. (pp. 397–407) have investigated the impact of obesity and overweight on quality of life and blood pressure control in hypertension, showing both obesity and overweight deteriorate blood pressure control, and obesity diminishes the physical versus mental components of quality of life regardless of sex. Bordicchia et al. (pp. 389–396) from investigations on human adipocytes conclude that the lower dysmetabolic effects of nebivolol in humans may depend on its β3 agonistic activity and the consequent induction of thermogenic program in adipocytes.

Together with the previously cited article by Schulz et al., other interesting studies have investigated the role of oxidative stress and inflammation in hypertension. Kim et al. (pp. 306–317) provide evidence that in the spontaneously hypertensive rat, endothelial nitric oxide synthase coupling can be regulated by NADPH:quinone oxidoreductase-1 (NQO1) activation via LKD1/AMPK/GTPCH-1 modulation and that β-lapachone-induced NQO1 activation lowers blood pressure. The authors advance the hypothesis that NQO1 might be a new therapeutic target in hypertension, an interesting hypothesis that is further discussed in an editorial commentary by Taben M. Hale (pp. 233–235), who comprehensively reviews the available evidence and concludes that future studies investigating the potential of the treatment approach based on NQO1 activation in protecting against hypertension-induced organ damage are warranted.

In a prospective study of primiparae with a history of early-onset preeclampsia, van Rijn et al. (pp. 408–414) have observed that recurrent preeclampsia in a next pregnancy is related to elevated prepregnancy levels of C-reactive protein and fibrinogen, thus supporting a role for inflammation in recurrent hypertension disorders of pregnancy. However, Julius et al. (pp. 251–259) analyzing data from the prospective interventional TRial of Preventing HYpertension (TROPHY), find that an inflammatory marker, increased white blood cell counts (WBCCs), did not predict incident hypertension, and candesartan, though reducing the rate of incident hypertension, did not alter WBCC. The authors conclude their findings do not support the hypothesis that inflammation contributes to incident hypertension. In an accompanying editorial, Ernesto L. Schiffrin (pp. 228–229) takes the opposite view and summarizes data favoring a role of inflammation and immunity in cardiovascular disease and in hypertension, and argues that a 4-year study such as TROPHY may not be long enough to unravel this role.

Carter et al. (pp. 339–351) have investigated the role of antioxidant availability and prostaglandins in endothelial dysfunction induced by ischemia reperfusion injury: antioxidant administration failed to preserve flow-mediated vasodilatation compared with control, and suppression of prostaglandin synthesis by ibuprofen produced the largest constrictive response. Another interesting pathophysiological study is published by Calò et al. (pp. 331–338). These authors by contrasting clinical conditions like hypertension and Bartter's and Gitelman's syndromes, show the importance of p63RhoGEF in angiotensin II-mediated signaling involved in blood pressure regulation.

As usual in the Journal, several articles deal with hypertension-related organ damage. In a thoughtful review, Yannoutsos et al. (pp. 216–224) discuss the respective role of macrovascular alterations, mostly consisting in arterial stiffening and disturbed wave reflection, and microvascular alterations for which endothelial dysfunction is an important precursor.

Concerning macrovascular alterations, Sommermeyer et al. (pp. 276–285) report that a photoplethysmographic pulse wave signal analyzer may provide recognition of individuals with high cardiovascular risk in the sleep laboratory, and Morra et al. (pp. 286–293) show that long-term resistant training in men is associated with decreased aortic stiffness and lower central augmentation pressure. Ding et al. (pp. 207–215) publish a review and meta-analysis of studies quantitatively assessing retinal microvessels and report that retinal arteriolar narrowing and venular widening are independently associated with increased risk of developing hypertension. In an accompanying review, Rizzoni and Muiesan (pp. 225–227) remark that the prognostic value of retinal arterioles to venular ratio remains a controversial issue, but quantification of these alterations may become a useful approach to the assessment of organ damage in hypertension. Ohara et al. (pp. 432–438) have investigated protein excretion in normoalbuminuric patients with diabetes, and report that the presence of hypertension further increases urinary excretion of immunoglobulin G, ceruloplasmin, and transferrin, which may reflect an increase in glomerular pressure. Johansson et al. (pp. 260–266), investigating interarm differences of blood pressure, have observed that exaggerated absolute diastolic (but not systolic) interarm blood pressure differences are associated with higher left ventricular mass and wall thickness. In a cross-sectional evaluation of nondialysis-dependent chronic kidney disease stage 3–5 patients, Cordero et al. (pp. 439–445) find that even in these patients, the electrocardiogram is a weak indicator of left ventricular hypertrophy, and conclude that this does not support the use of electrocardiography as a unique tool in the screening of left ventricular hypertrophy in patients with chronic kidney disease.

Four articles report epidemiological or large observational clinical studies. Kurioka et al. (pp. 236–244) in a large prospective study on progression to hypertension in nonhypertensive individuals confirm that normal or high normal blood pressure increases the risk of progression to hypertension, but report this risk is particularly high in individuals aged 20–34 years. Jae et al. (pp. 245–250) find that higher hematocrit levels, even within the normal range, are associated with the incidence of hypertension independent of other risk factors. Tsioufis et al. (pp. 415–422) have followed up 1911 hypertensive patients for a mean of 3.9 years and observed that patients with resistant hypertension at baseline remained resistant throughout the study period, with a cardiovascular risk twice as large as that in nonresistant hypertensive patients. Yano et al. (pp. 423–431) report the results of a prospective study on 585 elderly hypertensive patients followed up for 2.8 years, showing that cognitive dysfunction at baseline was an independent marker of cardiovascular disease events.

Finally, the Editor would like to call the Journal readers’ attention on a short report of the 3rd Annual International Society of Hypertension New Investigators Symposium: young investigators are needed to further develop research in our field and are the authors upon whom the Journal of Hypertension relies for its future.

Back to Top | Article Outline


Conflicts of interest

There are no conflicts of interest.

© 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins