Biomedical subjects

C Rasetti

Publications and source records attributed to C Rasetti.

7 recordsLinked to original sources

PubMed1999

Preliminary evaluation of 2-[4-[3-tert-butylamino)-2-hydroxypropoxy]phenyl]-3-methyl-6-me thoxy-4(3H)-quinazolinone ([+/-]HX-CH 44) as a selective beta1-adrenoceptor ligand for PET.

(+/-)-3-[11C]Methyl-2-[4-[3-(tert-butylamino)-2-hydroxypropoxy]phenyl]-6 -methoxy-4(3H) quinazolinone ([+/-]-[11C]HX-CH 44) was labeled with carbon-11 using [11C]iodomethane with the corresponding N-demethylated precursor. Then, 30-90 mCi (1.10-3.33 GBq) of pure [11C]HX-CH 44 were obtained 30 min after end of bombardment with specific radioactivities of 500-1,400 mCi/micromol (18.5-51.8 GBq/micromol). Myocardial uptake in dogs was 0.340+/-0.043 pmol/mL tissue per nanomole injected, 10-15 min postinjection. Heart-to-lung ratio was 3 from the 5th to the 30th minute. Only 35% of the myocardial radioactivity could be displaced. Tissue uptake could not be blocked with appropriate compounds. Therefore, (+/-)-[11C]HX-CH 44 does not appear to be a suitable ligand for the study of myocardial beta1-adrenoceptors in positron emission tomography.

Adrenergic beta-Antagonists↗

PubMed1996

Differences between cytokine effects in the microcirculation of the rat.

We studied by in vivo microscopy in rat cremaster muscle the acute and delayed effects of short exposure to tumor necrosis factor (TNF), interleukin (IL)-1 beta, and IL-6 on basal tone and vascular reactivity of second- to fourth-order arterioles (A2-A4). A 20-min exposure to recombinant human (rh) TNF (0.1-10 ng/ml) induced a significant arteriolar vasodilation, but no significant changes in basal tone were found after exposure to the same doses of IL-1 beta. In contrast, the same exposure to IL-6 (0.1-10 ng/ml) induced a significant dose-dependent vasoconstriction (i.e., 8, 15, and 21% at 10 ng/ml in A2-A4 arterioles, respectively). This vasoconstriction was inhibited by the thromboxane A2 receptor antagonist SQ-29548. We did not find any significant effect of rhTNF or IL-6 on vascular reactivity to norepinephrine immediately after exposure to these two cytokines or 100 min after the end of the exposure. Contrastingly, a large dose-dependent decrease in reactivity to norepinephrine was found immediately after exposure to IL-1 beta and still persisted 100 min after the end of the exposure. Such a decrease was not found for the vasoconstriction in response to KCl. We conclude that, at the microvascular level, large differences exist between the three cytokines generally considered to mediate the harmful cardiovascular effects in sepsis. 1) TNF but not IL-1 beta is responsible for a vasodilatory effect, whereas the effect of IL-6 is a thromboxane A2-mediated vasoconstriction. 2) Short exposure to IL-1 beta but not to rhTNF or IL-6 diminishes the response of the arterioles to norepinephrine but not to KCl.

Animals↗

PubMed1996

Effects of tumor necrosis factor and interleukin-1 on the constriction induced by angiotensin II in rat aorta.

To better understand the different steps in the changes occurring in vascular reactivity during sepsis, we studied the effects of a short exposure to tumor necrosis factor (TNF) and interleukin-1 (IL-1) on the contraction in response to angiotensin II (ANG II). The contraction elicited by ANG II was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 25 ng/ml TNF or to 5 or 20 ng/ml IL-1. This contraction was not significantly changed by TNF but was 109 +/- 23 and 190 +/- 38% greater than in control rings after 5 and 20 ng/ml IL-1, respectively. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that IL-1 interferes with this modulation. We found that the IL-1-induced increase in contraction in response to ANG II was completely inhibited by 10(-5) M of the cyclooxygenase inhibitor indomethacin and also by 10(-5) M of the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548. Note, however, that in rings exposed to IL-1 the contraction in response to the thromboxane A2-receptor agonist U-46619 was not significantly different from the contraction in unexposed rings. Furthermore, no loss was observed in either the vasodilator response to 10(-9)-10(-4) M of the endothelium-dependent-receptor agonist acetylcholine or in the receptor-independent contraction induced by 60 mM K+. We conclude that short exposure to IL-1, but not to TNF, produces a specific increase in the vasoconstrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This increase might result from an IL-1-induced shift in favor of constrictor prostanoids in the balance of the dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.

Acetylcholine↗

PubMed1995

Short exposure to endotoxin increases the constriction induced by angiotensin II in rat aorta.

The contraction elicited by angiotensin II (ANG II) was studied by using standard isometric tension techniques in aortic rings exposed for 1 h to 1 or 10 micrograms/ml Escherichia coli lipopolysaccharide endotoxin (LPS). This contraction was 18 and 71% greater for the two doses of LPS, respectively, than in unexposed control rings. In endothelium-denuded rings, the LPS-induced increase in contraction in response to ANG II was completely abolished. Because the contraction induced by ANG II is modulated by the simultaneous release of prostaglandins, we tested the hypothesis that LPS interferes with this modulation. We found that the LPS-induced increase in contraction to ANG II was inhibited in the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) or the prostaglandin H2/thromboxane A2-receptor antagonist SQ-29548 (2 x 10(-7) M). Conversely, the LPS-induced increase in contraction in response to ANG II was not inhibited by the presence of dexamethasone (10(-6) M), which inhibits new protein synthesis. In addition, there was no loss of vasodilator response to the endothelium-dependent receptor agonist acetylcholine (10(-8)-10(-4) M) or in the constrictor responses to norepinephrine (10(-9)-10(-5) M) and KCl (20-100 mM). We conclude that short exposure to LPS produces a specific increase in the constrictor response to ANG II via mechanisms mediated by prostaglandin H2/thromboxane A2. This effect could be a LPS-induced shift in favor of constrictor prostanoids in the balance of dilator/constrictor prostanoids, the release of which is associated with stimulation by ANG II.

Acetylcholine↗

PubMed1994

Magnesium modulates endothelial dysfunction produced by elevated glucose incubation.

In aorta taken from diabetic rabbits studied ex vivo or from normal rabbits exposed to increased glucose for 6 h in vitro the endothelium-dependent relaxation to acetylcholine (ACh) is impaired. Magnesium ion concentration influences vascular smooth muscle (VSM) contractility, endothelium-dependent relaxing factor (EDRF) release and prostaglandin production. We wished to determine the effects of changes in magnesium ion concentration on the abnormality induced by elevated glucose concentration (44 mM) in the endothelium-dependent responses observed in isolated rabbit aorta. In phenylephrine (PE)-precontracted vessels, with physiologic salt solution (PSS) containing 1.2 mM magnesium, endothelium-dependent relaxation and endothelium-independent contraction to ACh was not affected by incubation in elevated glucose (44 mM), indomethacin (10(-5) M) treatment, or both. In solution containing 0.6 mM magnesium, the endothelium-dependent relaxation to ACh was impaired in elevated glucose. Indomethacin treatment did not affect endothelium-dependent relaxation in the control solution but partially restored the response to ACh in elevated glucose. Under basal conditions and in the presence of nitric oxide (NO) synthase inhibition, ACh induced a contraction. In low magnesium-containing medium, this contraction was potentiated by the presence of endothelial cells in control (5.5 mM) and even more in elevated glucose concentration (44 mM). The endothelium-dependent contractions were abolished by pretreatment with indomethacin. However, in control magnesium conditions (1.2 mM), an endothelium-dependent component to the ACh contraction was observed only in elevated glucose concentration. Responses to sodium nitroprusside (SNP), KCI, and serotonin, and the concentration to ACh (in the absence of endothelium) were not influenced by elevated glucose, indomethacin treatment, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1994

ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension.

Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.

Animals↗

PubMed1993

[ANP changes induced by varying TSH].

Aim of our study was estimating if TSH could influence the timing of ANP release. About it we observed 70 male subjects: 40 were euthyroid patients aged 42 +/- 5 years (group A); 20 patients treated by thyroxine in doses sufficient for inhibiting TSH release, aged 45 +/- 7 years (group B). A third group (C) was composed by 10 subjects with high basal levels of serum T3 and T4 with no thyrostatic therapy, aged 40 +/- 9 years. These subjects underwent a TRH test estimating at -30', 0', 30', 60', 120' plasma concentrations of TSH, ANP, T3, T4. In reply to physiological stimulus induced on patients of group A we observed a significant increase of TSH values (max at 60') and ANP levels (max at 120'). No significant variations occurred during the TRH test in T3 and T4 concentrations. In groups B and C no important modifications were observed neither in TSH nor in ANP plasma levels. ANP secretion seems to be dependent from the secretory condition of hypothalamus-pituitary-thyroid axis both in physiological and pathological conditions.

Adult↗