Evidence for a vascular sensitizing factor in plasma of saline-loaded dogs.

Abstract

SUMMARY This study investigates whether plasma extracts previously demonstrated to have natriuretic and antinatriferic activity have effects on vascular reactivity of rat cremaster arterioles. Plasma from hydropenic and saline-loaded dogs was subjected to Diafiltration, and eluted on a strong cation exchange column (SCX). The effects of intraarterial injections of various column fractions on constrictor responses to repeated injections of 33.3 ng of norepinephrine (NE) were used to indicate changes in vascular responsiveness in third order cremaster arterioles. SCX fraction I (void volume) from saline-loaded dogs (FI-S) caused an increase in constrictor response to NE of 101 %. Increased vascular responsiveness peaked at 40 minutes and remained significantly elevated (p < 0.05) for 130 minutes. Fraction I from plasma of hydropenic dogs (FI-H) and fraction III from plasma of salineloaded dogs (FIII-S) did not increase vascular responsiveness to NE. FI-S shifted the dose response curves for NE, arginine vasopressin, and angiotensin II parallel and to the left relative to control by a factor of 3.05-, 2.95-, and 5.63-fold, respectively, at the 50% constrictor dose. Systemic injections of FI-S, but not FI-H, caused a 10 mm Hg rise in blood pressure at 50 minutes, and blood pressure was significantly elevated for 30 to 90 minutes after injection (p < 0.01).These data demonstrate a vascular-sensitizing factor in FI-S. The factor appears in the same chromatographic fraction previously demonstrated to contain natriuretic, antinatriferic, and digoxin-like activity. The correlation of these activities with salt loading suggests they are due to the same substance, which may be the putative natriuretic hormone. 3 demonstrated that hypertension could be transferred from a genetically salt-sensitive rat (S rat) to a salt-resistant rat (R rat) when both were joined in a parabiotic union and fed salt. Based on these experiments, Dahl et al. suggested that salt-induced hypertension might be caused by a low molecular weight,

Arteriolar reactivity to pressure stimuli in hamsters with renal hypertension.

“…The relation between volume expansion and arteriolar reactivity has not been established; however, there may be a link between the elevated blood volume and the release of a natriuretic compound that could alter vascular tone or mechanics, or both, and thus, alter reactivity to pressure. 38 Therefore, the increased blood volume in renal hypertension may have resulted in arteriolar autoregulation and vasoconstriction through a change in the mechanical properties or the sensitivity of the vascular smooth muscle to vasoactive stimuli.…”

Ouabain-Like Na+,K+-ATPase Inhibitory Activity of a Plasma Extract in Normal Pregnancy and Pregnancy Induced Hypertension.

“…A canine plasma extract that inhibits Na+,K+ ATPase released by volume expansion has been observed to have digoxin-like immuno reactivity (3), and the endogenous digitalis like substance increases sensitivity to the vaso constrictive effects of norepinephrine and angiotensin (4). Hamlyn et al (5) showed that the Na+,K±ATPase inhibitory activity of a plasma substance was related to the high blood pressure in subjects with essential hypertension and suggested the involvement of a circulating Na+ pump inhibitor in the gen esis of essential hypertension.…”

“…Digoxin-like immunoreactive sub stances in unpurified material are not neces sarily always the same as the substances with Na+,K+-ATPase inhibitory activity (14), but only one of the studies determined the Na+,K+-ATPase inhibitory activities of the substances (8). Unfortunately, even when the enzyme activity was assayed (4,8), the assay mixtures employed contained a high K+ con centration; under such a condition, the observed inhibitory activity would include the non-specific (i.e., non ouabain-like) inhibitory activity (15).…”

Potent vasoconstrictor responses to endogenous digitalis-like factor of isolated, perfused dog intermediate auricular arteries.

“…It has been assumed that EDLF has a vasoconstrictor property (Plunkett et al 1982;Soldin 1986). However, no report is available as to vasoconstrictor action of the natriuretic fraction in isolated vascular muscle preparation.…”