THE ROLE OF HIGH DIETARY SALT INTAKE IN DEVELOPMENT OF RESISTANT HYPERTENSION

This study investigated the role of changes in the expression of the cytochrome P-450 4A (CYP450-4A) enzymes that produce 20-hydroxyeicosatetraenoic acid (20-HETE) in modulating the responses of rat mesenteric resistance arteries to norepinephrine (NE) and reduced Po2 after short-term (3-day) changes in dietary salt intake. The CYP450-4A2, -4A3, and -4A8 isoforms were all detected by RT-PCR in arteries obtained from rats fed a high-salt (HS, 4% NaCl) diet, whereas only the CYP450-4A3 isoform was detected in vessels from rats fed a low-salt (LS, 0.4% NaCl) diet. Expression of the 51-kDa CYP450-4A protein was significantly increased by a HS diet. Inhibiting 20-HETE synthesis with 30 μM N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) reduced the vasoconstrictor response to NE in arteries obtained from rats fed either a LS or HS diet, but NE sensitivity after DDMS treatment was significantly lower in vessels from rats on a HS diet. DDMS treatment also restored the vasodilator response to reduced Po2 that was impaired in arteries from rats on a HS diet. These findings suggest that 1) a HS diet increases the expression of CYP450-4A enzymes in the mesenteric vasculature, 2) 20-HETE contributes to the vasoconstrictor response to NE in mesenteric resistance arteries, 3) the contribution of 20-HETE to the vasoconstrictor response to NE is greater in rats fed a HS diet than in rats fed a LS diet, and 4) upregulation of the production of 20-HETE contributes to the impaired dilation of mesenteric resistance arteries in response to hypoxia in rats fed a HS diet.

Download Full-text

Cardiotonic Steroids—A Possible Link Between High-Salt Diet and Organ Damage

International Journal of Molecular Sciences ◽

10.3390/ijms20030590 ◽

2019 ◽

Vol 20 (3) ◽

pp. 590 ◽

Cited By ~ 6

Author(s):

Aneta Paczula ◽

Andrzej Wiecek ◽

Grzegorz Piecha

Keyword(s):

Salt Intake ◽

Organ Damage ◽

Disability Adjusted Life Years ◽

Dietary Salt ◽

High Salt Diet ◽

Salt Diet ◽

Dietary Salt Intake ◽

Disability Adjusted Life ◽

Life Years

High dietary salt intake has been listed among the top ten risk factors for disability-adjusted life years. We discuss the role of endogenous cardiotonic steroids in mediating the dietary salt-induced hypertension and organ damage.

Download Full-text

Role of the Kidneys in Resistant Hypertension

International Journal of Hypertension ◽

10.4061/2011/143471 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 23

Author(s):

Z. Khawaja ◽

C. S. Wilcox

Keyword(s):

Resistant Hypertension ◽

Salt Intake ◽

Antihypertensive Drugs ◽

Critical Role ◽

Diuretic Therapy ◽

Extracellular Fluid ◽

Treatment Resistance ◽

Sodium Reabsorption ◽

Dietary Salt ◽

Dietary Salt Intake

Resistant hypertension is a failure to achieve goal BP (<140/90 mm Hg for the overall population and <130/80 mm Hg for those with diabetes mellitus or chronic kidney disease) in a patient who adheres to maximum tolerated doses of 3 antihypertensive drugs including a diuretic. The kidneys play a critical role in long-term regulation of blood pressure. Blunted pressure natriuresis, with resultant increase in extracellular fluid volume, is an important cause of resistant hypertension. Activation of the renin-angiotensin-aldosterone system, increased renal sympathetic nervous system activity and increased sodium reabsorption are important renal mechanisms. Successful treatment requires identification and reversal of lifestyle factors or drugs contributing to treatment resistance, diagnosis and appropriate treatment of secondary causes of hypertension, use of effective multidrug regimens and optimization of diuretic therapy. Since inappropriate renal salt retention underlies most cases of drug-resistant hypertension, the therapeutic focus should be on improving salt depleting therapy by assessing and, if necessary, reducing dietary salt intake, optimizing diuretic therapy, and adding a mineralocorticoid antagonist if there are no contraindications.

Download Full-text