Vascular contractile reactivity in hypotension due to reduced renal reabsorption of Na+ and restricted dietary Na+

Abstract

Reduced renal Na reabsorption along with restricted dietary Na depletes intravascular plasma volume which can then result in hypotension. Whether hypotension occurs and the magnitude of hypotension depends in part on compensatory angiotensin II-mediated increased vascular resistance. We investigated whether the ability of vascular resistance to mitigate the hypotension was compromised by decreased contractile reactivity. In vitro reactivity was investigated in aorta from mouse models of reduced renal Na reabsorption and restricted dietary Na associated with considerable hypotension and renin-angiotensin system activation: (1) the Na-Cl-Co-transporter (NCC) knockout (KO) with Na restricted diet (0.1%, 2 weeks) and (2) the relatively more severe pendrin (apical chloride/bicarbonate exchanger) and NCC double KO. Contractile sensitivity to KCl, phenylephrine, and/or U46619 remained unaltered in aorta from both models. Maximal KCl and phenylephrine contraction expressed as force/aorta length from NCC KO with Na-restricted diet remained unaltered, while in pendrin/NCC double KO were reduced to 49 and 64%, respectively. Wet weight of aorta from NCC KO with Na-restricted diet remained unaltered, while pendrin/NCC double KO was reduced to 67%, consistent with decreased medial width determined with Verhoeff-Van Gieson stain. These findings suggest that hypotension associated with severe intravascular volume depletion, as the result of decreased renal Na reabsorption, may in part be due to decreased contractile reactivity as a consequence of reduced vascular hypertrophy.

Role of the Renin Angiotensin System in Blood Pressure Allostasis-induced by Severe Food Restriction in Female Fischer rats

“…Similar observations were seen in a study of patients with AN compared to age-matched controls; patients with AN had to be infused with a higher concentration of Ang-[1–8] to achieve a 20 mmHg increase in BP 17 . Furthermore, in a mouse model of hypotension induced by severe intravascular volume depletion and decreased renal Na + reabsorption, aortic vessels exhibited decreased contractile reactivity 34 . This study suggested the cause of the reduced vasoconstriction was the reduced vascular hypertrophy.…”

The non-diuretic hypotensive effects of thiazides are enhanced during volume depletion states

“…Contractile experiments were performed as previously described [25, 26]. Experiments with thoracic aorta from NCC KO with normal salt diet and NCC KO with low salt diet were performed in parallel.…”

“…After 15 min, segments were again challenged with cumulative phenylephrine concentrations. Two of the constrictor responses to 50 mM KCl in aorta from NCC mice exposed to normal and low salt diet were utilized in pervious work [26]. …”

Metabolomics highlights biochemical perturbations occurring in the kidney and liver of mice administered a human dose of colistin

“…DA is a natriuretic hormone and regulates sodium levels, inducing sodium excretion and constraining its reabsorption at the proximal tubule ( Choi et al, 2015 ). Thus, excessive action of DA leads to limited levels of circulatory sodium, a condition that is linked with the occurrence of hypotension ( Alshahrani et al, 2017 ). Additionally, it has been speculated that impairment of the estimated glomerular filtration rate (eGFR) is associated with neurological adverse effects, i.e., the limited eGFR leads to increased circulation levels of uremic toxins and kidney hormones that end up in the dopaminergic system of the brain ( De Donato et al, 2022 ).…”