[INFLUENCE OF THE FEMALE SEX HORMONE 17-BETA-ESTRADIOL ON THE DEGREE OF HYPOXIC PULMONARY HYPERTENSION IN MALE AND FEMALE WISTAR RATS.]

The influence of endogenous and exogenous 17-beta-estradiol on the degree of hypoxic pulmonary hypertension (HPH) in male and female Wistar rats has been studied. Endogenous estradiol reduced the right ventricular systolic pressure (RVSP) in normal female rats, but not in male rats. Exogenous estradiol (15 pg/kg for 4 weeks) caused the same effect. The HPH was induced by exposure to intermittent hypobaric hypoxia (10 h a day, 02 = 10%). Two weeks after hypoxia exposure, increased RVSP was more developed in females as compared to males. Comparison of RVSP between hypertensive and normotensive fet'a- le groups showed that the pathology in hypertensive females with retained ovaries is developed more than in ovariectomized ones. Exogenous estradiol exhibi- ted no protective effect in hypoxic ovariectomized female rats. In males, the ovariectomy did not influence the RVSP level, but caused hypertrophy of the right ventricle. In this case, exogenous estradiol led to an increase in RVSP. Thus, endogenous 17-beta-estradiol has a protective effect on the pulmonary blood flow in normal females. In the case of hypoxic pulmonary hypertension, endogenous estradiol enhances the development of this pathology in females and ovariecto- mized males.

Effect of Chronic Administration of Estradiol on Responsiveness of Isolated Systemic and Pulmonary Blood Vessels from Ovariectomized Wistar Rats with Hypoxic Pulmonary Hypertension.

The long-term (4 weeks) administration of estradiol (15 µg/kg/day) to ovariectomized female Wistar rats induced hypoxic pulmonary hypertension and significantly (p<0.05) diminished relaxation of perfused serotonin-preconstricted isolated vascular segments of the pulmonary artery in response to estradiol (10(-6) M). At the same time, the isolated segments of systemic popliteal artery demonstrated a diminished response to serotonin and increased relaxation induced by acetylcholine (10(-5) M) or estradiol (10(-5) M) in comparison with preconstricted control vessels. Moderation of responsiveness to estradiol in pulmonary circulation can be one of the factors underlying the pro-hypertensive action of estradiol in female rats with hypoxic pulmonary hypertension.

[Intravenous injection of coenzyme Q10 increases its level in rat brain].

It is established that intravenous injection of solubilized coenzyme Q10 provides quick and lasting increase in its level in the brain as compared to control intact rats and those with cerebral ischemia. These new data provide a basis for studying the efficacy of coenzyme Q10 as a neuroprotective agent in ischemic stroke.

[Chronic administration of estrogen receptors antagonist reduces degree of hypoxia-induced pulmonary hypertension caused by chronic injections of estrogen in ovariectomised female Wistar rats].

As we showed previously, administration of estradiol in different doses (5 and 15 mcg per day for 21 day) initiates the development of pulmonary arterial hypertension (PAH) in ovariectomised female Wistar rats. The aim of current study was to analyze the involvement of antagonist of estrogen receptors type a- and beta- ICI 182,780 (fulvestrant) in development of hypoxia-induced pulmonary arterial hypertension. Ovariectomised female rats were separated into 5 groups received subcutaneously for 1 month : 1. Estrogen 15 mcg per day. 2. Estrogen 60 mcg per day 3. Antagonist of estrogen receptors type alpha- and beta- fulvestrant 150 mcg per day. 4. Estrogen 15 mcg/d + fulvestrant 150 mcg/d. 5. Propylenglycol as a control group. PAH was induced by exposure to hypobaric hypoxia. Rats were housed in a hypobaric chamber at simulated altitude of 5000 m, 10 h a day, 2 wk (O2 concentration reduced to 10%). We suppose that the development of pulmonary hypertension in ovariectomised female Wistar rats caused by administration of estrogen (15 mcg and 60 mcg per day for 1 month) is mediated by estrogen receptors type alpha- and beta-.

[Chronic administration of estradiol to ovariectomized female Wistar rats causes development of hypoxic pulmonary hypertension].

We have studied the role of female sex hormone estradiol in the development of hypoxic pulmonary arterial hypertension. Previously, it was shown that the development of pulmonary hypertension in Wistar female rats is accompanied by a twofold increase in the estradiol level. Ovariectomy reduces the degree of pulmonary hypertension in these animals. In this work, the effect of various chronic doses of exogenous estradiol (5 and 15 microg/kg per day) on the development of hypoxic pulmonary hypertension in Wistar female rats has been studied. Pulmonary hypertension was induced by exposure to hypobaric hypoxia (10 h a day for 2 weeks) at simulated altitude of 5000 m (O2 concentration reduced to 10%). The administration of estradiol in different doses (5 and 15 microg/kg per day) for 21 day initiated the development of pulmonary hypertension in ovariectomized Wistar female rats.

[Peripheral mechanisms of action of oxatriazolium-5-olate derivative 3-(3-[1,2,4]-triazolo)oxatriazolium-5-olate in spontaneously hypertensive rats].

It is shown that 3-(3-[1,2,4]-triazolo)-oxatriazolium-5-olate (azasidnon-6) can act directly on the vascular wall of isolated segments of caudal ventral artery of SHR rats. Using heme-dependent soluble guanyl cyclase inhibitor 1H-[1,2,4]-oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), it has been found that one of the possible mechanisms of azasidnon-6 vasodilatory action includes heme-dependent activation of a soluble form of guanylate cyclase.

[Role of estradiol in hypoxia-induced pulmonary hypertension in female rats].

Gender differences play role in pathogenesis and treatment of many cardiovascular diseases. One of these diseases is hypoxia-induced pulmonary hypertension (PHT). The aim of this study was to analyze the involvement of female hormone estradiol in development of hypoxia-induced PHT in female Wistar rats. PHT was induced by exposure to hypobaric hypoxia in an altitude chamber at a simulated altitude of 5000 m (02 concentration reduced to 10 %), 10 h per day for 2 weeks. The development of PHT leads to a twofold increase in the level of estradiol. Ovariectomy decreases by half the level of estradiol and causes significant decrease in hypoxia-induced PHT symptoms.

[Hypotensive effect of oxatriazolo-5-olate derivative in chronic experiments on SHR rats].

Long-term peroral administration of the oxatriazolo-5-olate derivative azasydnon-6 leads to a decrease in the systolic arterial blood pressure in SHR rats. The hypotensive effect of azasydnon-6 is mediated by stimulation of the sGC-cGMP pathway, which triggers vasodilatation of SMC in vessels. The drug effect is inhibited by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one, a selective sGC inhibitor. During long-term treatment, no tolerance to azasydnon-6 is developed in isolated arterial vessels.

Experimental study of hypotensive effect of kardos in rats with inherited hypertension.

Kardos, a preparation containing ultralow doses of antibodies to C-terminal fragment of type 1 receptor of angiotensin II, intragastrically administered to SHR rats with hereditary hypertension for 28 days reduced blood pressure by 14.8%. Kardos was not inferior to losartan and, in contrast to the latter reduced HR by 9.4%.

[Hypotensive effect of oxatriazolium-5-olate derivative].

Intravenous administration of azasidnon-6 (oxatriazolium-5-olate derivative) induces prolonged dose-dependent decrease in arterial blood pressure in awake Wistar and SHR rats. Hypotensive effects of azasidnon-6 in SHR rats is significantly higher during inhibition of endogenous NO synthesis.