α ₁ - and α ₂ -Adrenoceptor Control of Sodium Transport Reverses in Developing Hypertension

Abstract

Abstract-␣-Adrenergic receptor (AR) activation enhances sodium retention in certain forms of hypertension. The objective of the present study was to understand the role of ␣-ARs in regulating sodium transport by distal tubules (DT). DT cells were isolated from kidneys of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 6 weeks, when hypertension is developing, or at 12 weeks, when hypertension is established. The ␣ 1 -AR agonist phenylephrine increased 22 Na uptake by 50% into DT cells of 6-week SHR; no effect was observed with WKY cells. The ␣ 2 -AR agonist B-HT 933 increased uptake by only 10%. At 12 weeks, the pattern of ␣-AR regulation was reversed: ␣ 1 -AR-induced sodium uptake was only 15%, whereas ␣ 2 -AR activation increased sodium uptake by 35% in SHR and WKY cells. ␣ 1 -AR-induced sodium uptake in 6-week SHR cells was abolished by prazosin; ␣ 2 -AR-stimulated sodium uptake was blocked by yohimbine in 12-week SHR and WKY. Key Words: receptors, adrenergic Ⅲ blood pressure Ⅲ catecholamines Ⅲ epinephrine Ⅲ hypertension Ⅲ calcium Ⅲ norepinephrine O ne proposal for the initiation and maintenance of hypertension centers on a reduced capacity of the kidneys to excrete salt and water in proper relation to intake. 1 Sodium retention could initiate or contribute to the development of hypertension by activating mechanisms in vascular smooth muscle, the sympathetic nervous system, or expansion of effective extracellular fluid or plasma volume. 2,3 Chronic stimulation of renal nerves or intrarenal infusion of norepinephrine increases sodium retention and is capable of producing hypertension. 4,5 Conversely, renal denervation attenuates sodium retention and the onset of hypertension 6,7 but exerts only minimal effects in adult animals with established hypertension. 7,8 Metabolic balance studies examining the intake and excretion of sodium and water document that spontaneously hypertensive rats (SHR) between 4 to 7 weeks of age retain more sodium than do age-matched Wistar-Kyoto (WKY) rats. 2 During this period, urinary excretion was less in SHR than WKY rats and attributed to renal mechanisms. As the animals matured and systolic arterial pressure increased, renal sodium excretion was normalized in 8-to 13-week SHR. 9 These findings suggest that altered regulation of renal sodium absorption parallels the increase in pressure observed in SHR.The focus of this study was to test the hypothesis that ␣-adrenergic receptors (␣-ARs) contribute to the increased sodium absorption in distal tubule (DT) cells of SHR during developing hypertension (4 to 7 weeks). Renal nerves impinge directly on proximal tubules (PT) and DT. 10 Previous studies showed that ␣ 1 -and ␣ 2 -AR agonists stimulate Na ϩ /H ϩ exchange to a similar level in PT cells from SHR and WKY rats from 4 to 16 weeks of age. 11 It is predicted that ␣-ARs increase sodium absorption in DT cells. The mammalian DT is composed of 3 segments: distal convoluted tubule, connecting tubules, and initial cortical collecting duct. 12 In aggregate, these segm...

Tumor necrosis factor induces sodium retention in diabetic rats through sequential effects on distal tubule cells

“…Distal tubule cells were incubated with a primary antibody to Tamm-Horsfall protein covalently attached to a magnetic particle (Polysciences Inc, Warrington, PA, USA) and disassociated from other cell types by immunomagnetic separation [16]. Distal tubule cells isolated by this procedure exhibited characteristic distal tubule transport pathways, including calcitonin and parathyroid hormone-stimulated calcium transport [17,18], amiloride and chlorothiazide-sensitive sodium uptake [19], and phenylephrine-stimulated sodium transport [20] (Table 1). Sodium and calcium uptake was measured in distal tubule cells freshly isolated from control rats or in primary distal tubule cells cultured in 5 mmol/L glucose media for 10 days.…”

β‐Adrenergic‐AMPK Pathway Phosphorylates Acetyl‐CoA Carboxylase in a High‐epinephrine Rat Model, SPORTS

“…ARs occur in several isoforms, α‐ and β‐ARs. Because both α‐ and β‐ARs expressed in the vasculature and heart regulate vasoconstriction and cardiac functions, many agonists and antagonists of ARs have been used as therapeutic drugs for circulatory diseases such as hypertension, cardiac dysrhythmias, and myocardial infarction (1,2). In addition, β‐ARs have important roles in the regulation of energy metabolism, including energy expenditure and lipolysis (3).…”

Dynamics of GRK2 in the kidney: a putative mechanism for sepsis-associated kidney injury

“…The most up-to-date-version is available at https://doi.org/10.1042/CS20210462 CS-2021-0462-R2 pg 17 α1A, whereas vessels in general have the α1D subtype. Although we do not have evidence on how and whether tubular α adrenergic receptors would directly interfere in renal vascular tone, indirect effects due to its activation such as renin production/release, sodium handling, prostanoid secretion, potassium channel activation/inhibition and others, are conceivably putative mechanisms linking tubular α receptors and regulation of kidney tone (50)(51)(52).…”