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Biomedical subjects

G Bao

Publications and source records attributed to G Bao.

47 records · Page 3Linked to original sources

Angiotensin II induces the expression of c-fos mRNA in the central nervous system of the rat.

We have investigated the effects of intracerebroventricular injections of angiotensin II in conscious rats on the expression of c-fos messenger RNA (mRNA) in the caudate nucleus, hypothalamus, midbrain and brainstem using semi-quantitative polymerase chain reaction and Northern Blots. RNA analysis revealed the presence of c-fos transcripts in the midbrain and brainstem following icv injections of ANG II. ANG II (1, 10, 100 ng) induced a substantial increase in c-fos mRNA in the brainstem which was significant after 10 ng ANG II, and less after 100 ng. This effect was time-dependent being detectable within 15 minutes and maximal after 60 minutes. This ANG II-induced c-fos mRNA expression was totally inhibited by icv pretreatment with the ANG II-AT1 receptor antagonist, losartan. Our data show for the first time that stimulation of central periventricular AT1 receptors induces the expression of c-fos mRNA in the brain. Thus, ANG II, in addition to its short-term regulatory actions, can participate through transcription factors in neuroplastic processes.

Angiotensin II↗

Moexipril, a new angiotensin-converting enzyme (ACE) inhibitor: pharmacological characterization and comparison with enalapril.

The pharmacodynamic profile of the new angiotensin-converting enzyme (ACE) inhibitor moexipril and its active diacid, moexiprilat, was studied in vitro and in vivo. In vitro, moexiprilat exhibited a higher inhibitory potency than enalaprilat against both plasma ACE and purified ACE from rabbit lung. Upon oral administration of moexipril (10 mg/kg/day) to spontaneously hypertensive rats, plasma angiotensin II concentration decreased to undetectable levels, plasma ACE activity was inhibited by 98% and plasma angiotensin I concentration increased 8.6-fold 1 h after dosing. At 24 h, plasma angiotensin I and angiotensin II concentrations had returned to pretreatment levels, whereas plasma ACE activity was still inhibited by 56%. Four-week oral administration of moexipril (0.1-30 mg/kg/day) to spontaneously hypertensive rats lowered blood pressure and differentially inhibited ACE activity in plasma, lung, aorta, heart and kidney in a dose-dependent fashion. Equidose treatment (10 mg/kg/day) with moexipril and enalapril over 4 weeks led to comparable decreases in blood pressure, inhibition of plasma ACE and reduction of plasma angiotensinogen and to a similar attenuation of the pressor responses to angiotensin I and potentiation of the depressor responses to bradykinin. In contrast, ACE inhibition in aorta, heart and lung was significantly greater with moexipril than with enalapril, whereas in the kidney both drugs inhibited ACE activity to a similar extent. In summary, moexipril is an orally active ACE inhibitor that is comparable to enalapril in potency and duration of antihypertensive activity. The results of the present study demonstrate that 1) the antihypertensive potency of a given ACE inhibitor cannot be predicted from its in vitro characteristics and 2) the degree of blood pressure reduction does not correlate with tissue ACE inhibition.

Angiotensin I↗

[Effect of arginine on lymphocyte responses to ConA in burned mice].

It is well accepted that nutritional support improves the immunologic functions in burned patients. Arginine has been demonstrated to have tissue-specific properties which induce beneficial effects upon the immune system. A series of experiments are carried out, in order to evaluate the immune effect of arginine on burned mice. 1. Lymphocytes from both burned and unburned mice are harvested and incubated in various concentrations of arginine solution for 72 hours, and ConA-stimulating lymphocyte transformation is determined after incubation. 2. Burned animals are divided into four groups. Standard diets for nutritional support are formulated. These formulas contain an identical carbohydrate and lipid (61% and 15% of total energy respectively) intake with varied proportions of protein for each group (24%, 23%, 22%, and 20% of total energy, respectively), in addition. 0%, 1%, 2% and 4% of protein energy is supplied by arginine for different groups. Lymphocyte proliferations in responses to ConA stimulation are determined on the 7th postburn day. The data shows that, in vitro study, increasing arginine concentrations enhanced lymphocyte responses to ConA. The arginine needed level for optimal lymphocyte responses is 1.8 mmol/L in burned mice and 0.9 mmol/L in unburned controls. This difference indicates that in burned mice, a higher arginine concentration is required for better lymphocyte responses. On the contrary, further increase of arginine concentration do not give better response. When varied amounts of arginine are given in the diet to the burned mice, the degree of lymphocyte response to ConA is different. The amount of arginine which supplies 2% of total energy is found to be optimal.

Animals↗

[Inhibition of oxygen free radicals in potassium channels of cardiac myocytes and the action of salvianolic acid A].

By using the patch clamp technique, the effect of oxygen free radicals on the single potassium channels of cardiac papillary muscle cells were studied, as well as the action of salvianolic acid A. It was found that xanthane-xanthane oxidase generated oxygen free radicals could apparently inhibited the unitary currents of the single potassium channel activity. This inhibition was reversed by salvianolic acid A, which is an effective component extracted from Salvia miltiorrhiza.

Animals↗

[Intraoperative explosive choroidal hemorrhage (report of four cases)].

Intraoperative explosive choroidal hemorrhage (ECH) is a rare, but severe complication of intraocular surgery. This complication often occurs during or after intraocular surgery. We report four cases that developed this complication during surgery. Once the complication occurs, we should use the dehydration medicine intravenously, suture the incision, application of pressure directly to the eye and incise the postsclera. If the bleeding can't be stopped, enucleation is the indication.

Aged↗

Chronic kinin receptor blockade attenuates the antihypertensive effect of ramipril.

The contribution of endogenous kinins to the chronic antihypertensive effect of angiotensin converting enzyme inhibitors was investigated in two-kidney, one clip hypertensive Wistar rats, using the new bradykinin B2-receptor antagonist HOE 140 (D-Arg, [Hyp3, Thi5, D-Tic7, Oic8]-bradykinin). In a first protocol, rats were pretreated orally with the angiotensin converting enzyme inhibitor ramipril (1 mg/kg per day), for 4 weeks. Acute blockade of bradykinin receptors by intravenous injections of HOE 140 at doses of 8.4 and 100 micrograms/kg, which inhibited the depressor responses to exogenous bradykinin, did not affect the antihypertensive effect of ramipril in these animals. Bradykinin receptors were then blocked chronically by subcutaneous infusion of HOE 140 (500 micrograms/kg per day) via osmotic minipumps for 6 weeks, while ramipril treatment was continued. HOE 140 partially reversed the antihypertensive effect of ramipril from 115.3 +/- 4.6 to 123.8 +/- 3.3 mm Hg (mean arterial blood pressure) after 3 weeks and to 121.3 +/- 2.9 mm Hg after 6 weeks. In contrast, in controls (ramipril plus subcutaneous vehicle infusion) mean arterial blood pressure decreased further from 112.0 +/- 6.0 to 110.3 +/- 4.9 mm Hg after 3 weeks and to 103.7 +/- 5.0 mm Hg after 6 weeks (p less than 0.05 and p less than 0.01, HOE 140 versus controls). Plasma catecholamines were not significantly different between the two groups at the end of the experiment, indicating that the partial reversal of the antihypertensive effect was not due to a bradykinin-like agonistic effect on catecholamine release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Role of bradykinin in chronic antihypertensive actions of ramipril in different hypertension models.

We investigated the chronic effect of bradykinin B2-receptor blockade on the antihypertensive actions of the angiotensin-converting enzyme (ACE) inhibitor ramipril in three different hypertensive rat models, the two-kidney/one-clip (2K1C) hypertensive Wistar rat, the kinin-deficient 2K1C hypertensive Brown Norway Katholieke (BN-K) rat, and the spontaneously hypertensive rat (SHR). Chronic blockade of bradykinin B2 receptors by subcutaneous infusion of the new bradykinin antagonist HOE 140 (500 micrograms/kg/day) attenuated the antihypertensive effect of ramipril only in 2K1C hypertensive Wistar rats, but not in 2K1C BN-K rats and SHR. Our data demonstrate for the first time that potentiation of endogenous kinins contributes to chronic antihypertensive actions of ACE inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.

Animals↗

Kinin contribution to chronic antihypertensive actions of ACE-inhibitors in hypertensive rats.

The contribution of endogenous bradykinin to the chronic antihypertensive actions of the ACE-inhibitor, ramipril, was investigated in 2-kidney 1 clip (2K1C) hypertensive kinin-deficient Brown Norway Katholieke rats (BN-K) and 2K1C hypertensive Wistar rats (WI) as well as in spontaneously hypertensive rats (SHR). Treatment with ramipril plus the BK B2-receptor antagonist HOE 140 for 6 weeks significantly attenuated the antihypertensive effects of the ACE-inhibitor in 2K1C hypertensive WI rats, but not in 2K1C hypertensive BN-K rats and in SHR. Our data support the hypothesis that potentiation of endogenous kinins contributes to the chronic antihypertensive actions of ACE-inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.

Animals↗

HOE 140, a new highly potent and long-acting bradykinin antagonist in conscious rats.

The inhibitory effects of the new bradykinin antagonist HOE 140 (D-Arg-Arg-Pro-Hyp-Gly-Thi-Ser-D-Tic-Oic-Arg) on depressor responses to exogenous bradykinin were investigated in conscious rats and compared with those of the bradykinin antagonist B4146 (D-Arg-Hyp-Pro-Gly-Thi-Ser-D-Pro-Thi-Arg). HOE 140 showed a 250-700-fold higher potency in vivo and a much longer biological half-life than B4146. Plasma catecholamines were not increased after application of HOE 140, indicating that this compound did not interfere with catecholamine release. HOE 140 proved to be a highly potent, specific and long-acting bradykinin B2-receptor antagonist.

Amino Acid Sequence↗

Investigating the secretory pathway of the baculovirus-insect cell system using a secretory green fluorescent protein.

The secretory pathway is important in actively transporting proteins into the extracellular environment of eucaryotic cells. In this study a green fluorescent protein (GFP) mutant engineered to contain a secretion signal was used as a model protein in order to visualize the secretion process inside insect cells. Fluorescent microscopy indicated that significant amounts of secreted green fluorescent protein (sGFP) accumulated in High-Five, Trichoplusia ni, cells following infection with a baculovirus vector containing the gene under the polyhedrin promoter. Laser scanning confocal microscopy was used to reconstruct whole cell images of the infected High-Five cells at multiple days postinfection. While the protein was widely distributed at 2 days postinfection, certain intracellular regions appeared to contain higher or lower concentrations of the sGFP. A layer by layer examination indicated pockets in which sGFP was absent, and these appear to be vesicles that have recently released the sGFP or are not yet accumulating sGFP. By 3 days postinfection, the sGFP in some cells was concentrated in a number of widely dispersed globules, which may represent the vesicle remnants of a deteriorating secretory pathway. In contrast, nonsecreted GFP was more uniformly distributed in the cells than sGFP and did not accumulate in vesicles. In addition to GFP, the lectins wheat germ agglutinin (WGA) and concanavalin A (ConA), which have affinities for sugar residues, were used to examine the secretory pathway. The WGA, which is a Golgi marker, was distributed around the nucleus prior to infection but then was found to be polarized in one region of the cell following the baculovirus infection. The expansion of other cellular compartments following the baculovirus infection may have caused a change in intracellular distribution of the Golgi. While some of the sGFP was found to colocalize with the WGA label, much of the sGFP was outside this Golgi region. In contrast, ConA labeling, which was not as specific as WGA, was found throughout the cell both before and after infection similar to the sGFP distribution. These studies demonstrate that confocal visualization of fluorescent proteins can be used as an in vivo tool for examining secretory processing in insect cells.

Animals↗