Hypertension as a Metabolic Disorder and the Novel Role of the Gut

Masami Tanaka, Hiroshi Itoh

Research output: Contribution to journalReview article

Abstract

Purpose of Review: Hypertension is related to impaired metabolic homeostasis and can be regarded as a metabolic disorder. This review presents possible mechanisms by which metabolic disorders increase blood pressure (BP) and discusses the importance of the gut as a novel modulator of BP. Recent Findings: Obesity and high salt intake are major risk factors for hypertension. There is a hypothesis of “salt-induced obesity”; i.e., high salt intake may tie to obesity. Heightened sympathetic nervous system (SNS) activity, especially in the kidney and brain, increases BP in obese patients. Adipokines, including adiponectin and leptin, and renin-angiotensin-aldosterone system (RAAS) contribute to hypertension. Adiponectin induced by a high-salt diet may decrease sodium/glucose cotransporter (SGLT) 2 expression in the kidney, which results in reducing BP. High salt can change secretions of adipokines and RAAS-related components. Evidence has been accumulating linking the gastrointestinal tract to BP. Glucagon-like peptide-1 (GLP-1) and ghrelin decrease BP in both rodents and humans. The sweet taste receptor in enteroendocrine cells increases SGLT1 expression and stimulates sodium/glucose absorption. Roux-en-Y gastric bypass improves glycemic and BP control due to reducing the activity of SGLT1. Na/H exchanger isoform 3 (NHE3) increases BP by stimulating the intestinal absorption of sodium. Gastrin functions as an intestinal sodium taste sensor and inhibits NHE3 activity. Intestinal mineralocorticoid receptors also regulate sodium absorption and BP due to changing ENaC activity. Gastric sensing of sodium induces natriuresis, and gastric distension increases BP. Changes in the composition and function of gut microbiota contribute to hypertension. A high-salt/fat diet may disrupt the gut barrier, which results in systemic inflammation, insulin resistance, and increased BP. Gut microbiota regulates BP by secreting vasoactive hormones and short-chain fatty acids. BP-lowering effects of probiotics and antibiotics have been reported. Bariatric surgery improves metabolic disorders and hypertension due to increasing GLP-1 secretion, decreasing leptin secretion and SNS activity, and changing gut microbiome composition. Strategies targeting the gastrointestinal system may be therapeutic options for improving metabolic abnormalities and reducing BP in humans. Summary: SNS, brain, adipocytes, RAAS, the kidney, the gastrointestinal tract, and microbiota play important roles in regulating BP. Most notably, the gut could be a novel target for treatment of hypertension as a metabolic disorder.

Original languageEnglish
Article number63
JournalCurrent Hypertension Reports
Volume21
Issue number8
DOIs
Publication statusPublished - 2019 Aug 1

Fingerprint

Blood Pressure
Hypertension
Salts
Sodium
Sympathetic Nervous System
Renin-Angiotensin System
Sodium-Hydrogen Antiporter
Adipokines
Glucagon-Like Peptide 1
Obesity
Adiponectin
Leptin
Kidney
Gastrointestinal Tract
Stomach
Protein Isoforms
Sodium-Glucose Transport Proteins
Enteroendocrine Cells
Mineralocorticoid Receptors
Natriuresis

Keywords

  • Adipokines
  • Gastrointestinal tract
  • Hypertension
  • Microbiota
  • Obesity
  • Renin-angiotensin-aldosterone system
  • Salt
  • Sodium/glucose cotransporter
  • Sympathetic nervous activity

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Hypertension as a Metabolic Disorder and the Novel Role of the Gut. / Tanaka, Masami; Itoh, Hiroshi.

In: Current Hypertension Reports, Vol. 21, No. 8, 63, 01.08.2019.

Research output: Contribution to journalReview article

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