PubMed · 4326846
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S A Seligman. 1971. Baroreceptor reflex function in pre-eclampsia.. https://doi.org/10.1111/j.1471-0528.1971.tb00294.x
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Congestive heart failure (CHF) is characterized by sympathetic activation and parasympathetic withdrawal, and the magnitude of sympathoneural activation is associated with adverse outcome. Angiotensin-converting enzyme inhibitor therapy has been shown to reduce mortality and improve prognosis in patients with CHF, but whether this therapy improves cardiac autonomic control is not well known. This double-blind, placebo-controlled, crossover study examines the effects of enalapril on autonomic control in 12 patients with mild to moderate CHF by heart rate variability analysis. Compared with placebo, enalapril increased the SD of all normal RR intervals (SDNN) from 39 +/- 13 to 48 +/- 15 ms (p < 0.01), the SD of the average RR intervals for all 5-minute segments from 33 +/- 12 to 42 +/- 15 ms (p < 0.01), and the mean of the SDs of all RR intervals for all 5-minute segments (SDNN index) from 19 +/- 5 to 23 +/- 6 ms (p < 0.01). The root-mean-square successive differences and the percent differences between adjacent RR intervals > 50 ms were also increased from 17 +/- 8 to 21 +/- 8 ms (p < 0.01) and from 1.1 +/- 2.1 to 2.8 +/- 2.9% (p < 0.05). In addition, total, low-frequency, and high-frequency power were increased from 560 +/- 349 to 786 +/- 504 ms2/Hz (p < 0.01), from 125 +/- 107 to 179 +/- 135 ms2/Hz (p < 0.01), and from 46 +/- 32 to 94 +/- 78 ms2/Hz (p < 0.01), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
A series of 4-(heteroarylthio)-2-biphenylyltetrazoles was prepared, and the compounds were examined for their ability to displace [3H]AII from angiotensin II receptors. Analogues that exhibited significant receptor binding affinities at less than 10 microM were investigated further for potential antagonism of angiotensin II-mediated contraction of rabbit isolated aortic rings. Three 4-(heteroarylthio)-2-biphenylyltetrazoles were identified that exhibited sub-micromolar angiotensin II receptor binding affinities. These compounds and two reference agents, saralasin and losartan (DUP-753), exhibited concentration-dependent reversal of angiotensin II contraction in isolated aortic rings parallel to their receptor binding affinities. Molecular modeling studies were conducted to examine the conformational effects of the novel sulfide bridging unit contained in these 4-(heteroarylthio)-2-biphenylyltetrazoles. The biological effects of the sulfide bridge as well as alterations in the heteroaromatic moiety were investigated, and the resulting structure--activity relationships are discussed.
The rat angiotensin II type 2 receptor (AT2-R) expression was markedly downregulated by the mitogenic action of serum, growth factors and dexamethasone. The regulation by serum or growth factors did not affect the AT2-R mRNA half-life (18 h), whereas the AT2-R half-lives of dexamethasone-treated cells and proliferating cells decreased to 10 h and 15 h, respectively. Nuclear run-off assays indicated the mechanism of repression of AT2-R expression by serum, growth factors and dexamethasone or in proliferating cells to be, in large part, transcriptional. These findings indicate that transcription of the AT2-R gene is regulated in a growth state-dependent manner and suggest that this regulation provides a means by which cells can modulate their responsiveness to the actions of angiotensin II mediated through AT2-R.