Effects of 17beta-estradiol on the baroreflex control of sympathetic activity in conscious ovariectomized rats.

The effects of chronic treatment with 17beta-estradiol on baroreflex control of sympathetic activity were examined in conscious unrestrained ovariectomized rats. Baroreflex function was evaluated by logistic sigmoidal analysis of the relationships between changes in mean arterial pressure (MABP) and changes in heart rate (HR) and splanchnic nerve activity (SNA) when MABP was rapidly increased to 150 mmHg by intravenous phenylephrine after its reduction to 50 mmHg by intravenous nitroprusside. These baroreflex function curves were similar in vehicle- and estradiol-treated rats. However, after a 30-min infusion of vasopressin in vehicle-treated rats, the curve for HR was shifted downward, and the upper plateau and maximum gain for the SNA curve were reduced. These effects were abolished by estradiol. A 30-min phenylephrine infusion had no effect on the baroreflex curves. Thus estrogen can modulate the action of vasopressin on baroreflex control of sympathetic outflow and thereby participate in cardiovascular regulation.

Effects of 17beta-estradiol on sympathetic activity and pressor response to phenylephrine in ovariectomized rats.

The effects of 17beta-estradiol (E2) on sympathetic activity were examined in conscious unrestrained ovariectomized rats, instrumented under methohexital anesthesia to record mean arterial pressure (MABP), heart rate (HR), renal nerve activity (RNA), and splanchnic nerve activity (SNA) 1 day before the experiment. Injection of E2 (150 micrograms/kg iv) caused reductions (P < 0.01) in RNA (29 +/- 6%), SNA (25 +/- 2%), and HR (26 +/- 5 beats/min) within 20 min, but MABP remained unchanged. Ninety minutes after intravenous injection of E2 or vehicle, intravenous infusion of phenylephrine (PE; 6.2 micrograms . min-1 . kg-1) induced similar increases in MABP and decreases in HR, RNA, and SNA in both groups. By contrast, in rats chronically treated with E2, the pressor response to PE was smaller (P < 0.01; 22 +/- 5 mmHg) than in vehicle-treated rats (40 +/- 4 mmHg). The changes in HR, RNA, and SNA were similar in both groups, but the ratios of changes in HR and SNA to MABP, an index of baroreflex sensitivity, were greater in the E2-treated rats. These findings suggest that E2 can act centrally to modulate sympathetic function and thereby participate in cardiovascular regulation.

Sexual dimorphism in regional blood flow responses to vasopressin in conscious rats.

The greater pressor response to vasopressin in male than in nonestrous female rats results from a greater increase in total peripheral resistance in males. The present study was performed to identify the vascular beds that contribute to this difference. Mean arterial blood pressure (MABP) and changes in blood flow in the mesenteric and renal arteries and terminal aorta were measured in conscious male and nonestrous female rats 3 h after surgery. Graded intravenous infusions of vasopressin induced greater increases in MABP and mesenteric vascular resistance and a greater decrease in mesenteric blood flow in males. Vasopressin also increased renal vascular resistance to a greater extent in males. Because renal blood flow remained unchanged, this difference may be due to autoregulation. The vasopressin-induced reduction in blood flow and increased resistance in the hindquarters were moderate and did not differ between sexes. Thus the greater vasoconstrictor response to vasopressin in the mesenteric vascular bed of male than nonestrous females contributed importantly to the sexually dimorphic pressor response to vasopressin in these experiments.

Sex differences in the cardiovascular and renal actions of vasopressin in conscious rats.

The present study was carried out to investigate whether prostaglandins (PG) are involved in the mechanism that contributes to the sex difference in the antidiuretic and pressor actions of vasopressin. The experiments were performed in conscious male and nonestrous female rats. In hydrated rats, the graded infusion of vasopressin (10-1,000 pg.min 1.kg body wt-1) resulted in a dose-dependent antidiuresis: decreases in urine flow and free water clearance and an increase in urine osmolality. These responses were significantly greater in male than in nonestrous female rats. Pretreatment with a cyclooxygenase inhibitor, indomethacin (10 mg/kg body wt iv), significantly enhanced the antidiuretic response to vasopressin in both sexes. However, the magnitude of this enhancement was greater in female than in male rats. Thus indomethacin abolished the sex difference in the antidiuretic response to vasopressin. In a separate experiment in rats without water hydration and urine collection, infusion of pressor doses of vasopressin (1,000-6,000 pg.min-1.kg body wt-1) resulted in a greater increase in blood pressure in male than in nonestrous female rats. Treatment with indomethacin enhanced this response equivalently in both sexes and thus did not affect the sex difference in the pressor action of vasopressin. These data indicate that renal PG may mediate, at least in part, the sex difference in the antidiuretic action of vasopressin, whereas vascular PG seem not to play an important role in the sex difference in the pressor action of vasopressin.

Gonadal hormones modulate deoxycorticosterone-salt hypertension in male and female rats.

We have shown previously that, in rats with deoxycorticosterone (DOC)-salt hypertension, arterial blood pressure rises more rapidly and reaches a higher level in male than in female rats and that the course of the hypertension was ameliorated by gonadectomy in male rats and exacerbated by gonadectomy in female rats. The present investigation was undertaken to examine the role of the gonadal steroid hormones in modulating the course of DOC-salt hypertension in the rat. Our previous findings with respect to the effects of gender and gonadectomy on DOC-salt hypertension were confirmed in this study. Chronic treatment with gonadal steroids was begun 1 week before the start of the DOC-salt protocol. 17 beta-Estradiol attenuated the course of the hypertension in intact male rats and in gonadectomized females. Testosterone exacerbated the development of the hypertension in gonadectomized male rats but was without effect in intact females. Progesterone alone had no effect on the hypertension in ovariectomized rats but when given to ovariectomized rats in combination with estradiol transiently prevented the ameliorating effect of the estradiol. These effects of the gonadal steroid hormones could not be attributed to effects of saline intake. Thus, these findings demonstrate that the gonadal steroid hormones play an important role in modulating the pathogenesis of DOC-salt hypertension in the rat. It is suggested that the effects of the gonadal hormones on the course of the hypertension may be due to modulation of the cardiovascular and renal actions of vasopressin, since vasopressin is required for this model of hypertension.

European medical schools and tobacco.

Following a survey in 19 European countries of the habits, attitudes and knowledge of medical students regarding tobacco, World Health Organisation European Office and the International Union against Tuberculosis and Lung Disease jointly circulated to the Deans of all European medical schools a summary of the results, including figures for mortality for smoking-related diseases in their countries and a brief questionnaire concerning faculty action on the tobacco problem. The response rate was just over 50%, higher in Northern Europe (66%) than in Southern (35%) or Eastern (38%). Only 8% of faculties had a specific teaching module on tobacco. In most it was either systematically (35%) or unsystematically (55%) integrated in other teaching. Teaching hospitals, teaching areas and faculty meetings were said to be smokefree by over 90%; figures were lower for other areas. Seventy-seven per cent of Deans intended to discuss our approach with their teaching staff; 72% gave the name of a staff member with a particular tobacco interest.

Central vasopressin blockade enhances its peripheral release in response to peripheral osmotic stimulation in conscious rats.

Increased plasma osmolality results in increased central as well as peripheral release of vasopressin. Experiments were carried out to determine whether, in this circumstance, vasopressin can act centrally to modulate its peripheral release. Prior to the start of a thirty-min i.v. infusion of 2.5 M or 0.15 M NaCl, the rats were given an intracerebroventricular (i.c.v.) injection of a peptide V1/V2 vasopressin antagonist (2 micrograms), OPC-31260 (60 micrograms), a non-peptide V2 antagonist, or 1-desamino-8-D-arginine vasopressin (dDAVP, 5 ng), a V2 agonist. Experiments with the peptide antagonist were carried out in male and non-estrous female rats. Since there were no differences between males and females in the measured responses, experiments with the other two drugs were carried out only in males. Pretreatment with either the V1/V2 antagonist or the V2 antagonist enhanced the increase in plasma vasopressin levels in response to the hypertonic saline infusion by about 50% at the end of 30 min. dDAVP, on the other hand, had no effect. None of the i.c.v. drugs had an affect on either the pressor or bradycardic responses to hypertonic saline infusion. These observations suggest that vasopressin can act centrally in a negative feedback fashion to attenuate its own release into the peripheral circulation in response to increased plasma osmolality.

Sex difference in urinary concentrating ability of rats with water deprivation.

Our previous demonstration of sexual dimorphism in the antidiuretic response to exogenous vasopressin prompted us to investigate the response to moderately high levels of endogenous vasopressin stimulated by water deprivation in conscious rats. After 24 h water deprivation, urine flow was significantly higher and urine osmolality lower in females than in males. Plasma concentrations of vasopressin were higher in females than in males after water deprivation, but plasma osmolality did not differ. Gonadectomy, which had no effect in dehydrated males, decreased urine flow and increased urine osmolality in females to levels observed in intact and gonadectomized males. Spontaneous water intake was also measured and found to be lower in males and estrous females than in females in the other phases of the estrous cycle. These observations support the concept that there is a gender difference in the antidiuretic responsiveness to endogenous vasopressin, that this difference is dependent upon the ovarian hormones, and that it may lead to differences in consumptive behavior.

V2-receptor blockade enhances pressor response to vasopressin: gender difference.

The present study was performed to determine if the attenuated pressor response to vasopressin in conscious non-estrous female rats is due in part to an enhanced V2-like receptor vasodilator action. In male rats, infusion of vasopressin at a rate of 1 ng.min(-1).kg body weight-1 (wt) resulted in an increase in mean arterial blood pressure (MABP) of about 20 mm Hg. Thirty minutes after beginning the infusion of vasopressin, the iv bolus injection of a non-peptide V2-receptor antagonist, OPC-31260 (2 mg.kg body wt-1), resulted in a further gradual increase in MABP of approximately 8 mm Hg in the next 60 min (p < 0.05). Thus, the pressor response to vasopressin was greater in OPC-31260-treated than in vehicle-treated male rats (p < 0.01). The pressor response to vasopressin 30 min after the start of its infusion was lower (about 8 mm Hg) in non-estrous female rats than in males. During the next 60 min of vasopressin infusion, there was a small further increase (p < 0.05) in MABP in the females given either OPC-31260 or its saline vehicle. In contrast to the male rats, however, there was no difference in MABP between the OPC-31260 and vehicle treated females. Thus, the present study has provided additional evidence for a V2-like receptor related vasodilator effect in male rats. However, since female rats do not appear to express a V2-receptor mediated vasodilator response, the sexually dimorphic pressor response to vasopressin cannot be due to a gender difference in V2-receptor vasodilator activity.

Tobacco: a future disaster for Turkey's children.

Limited data from Turkey indicate that smoking presents a major threat to Turkish children. Parental, particularly maternal, smoking results in an increase in spontaneous abortion, low birth weight, congenital abnormalities, neonatal death and decreased physical and mental development in the infant, which can persist into adult life. Parental smoking results in increased rates of respiratory and middle ear illness in children, more so in infants and in older children more school absences. Naturally both of the effects are even greater if the children start to smoke themselves. Smoking parents are more likely to have smoking children, so that the cycle of illness repeats in future generations. Doctors have a major responsibility to save both present and future generations from this disaster. In this article appropriate action is outlined.

Tobacco and the developing world.

Tobacco consumption is increasing in developing countries, which will bear the brunt of the tobacco epidemic in the 21st century. If current smoking patterns continue, 7 of the world's 10 million annual deaths from tobacco in 2025 will occur in developing countries. Compared with developed countries, more men and fewer women currently smoke in developing countries, but smoking among girls and women is increasing. While indigenous tobacco production and consumption remain a major problem, of particular concern is the penetration by the transnational tobacco companies, bringing with them denial of the health evidence, sophisticated advertising and promotion, threats of trade sanctions based on tobacco trade, and opposition to tobacco control measures, in particular promotional bans and tobacco tax policy. Developing countries must urgently devise and implement national tobacco control policies, but many governments have little experience in the new noncommunicable disease epidemic or in countering the transnational tobacco companies.

Effects of gender on the central actions of neuropeptide Y and norepinephrine on vasopressin and blood pressure in the rat.

Neuropeptide Y (NPY) and norepinephrine are co-localized in the noradrenergic projection from the A1 nucleus of the medulla to the vasopressinergic magnocellular neurons of the supraoptic and paraventricular nuclei. Because this pathway is involved in the control of vasopressin release, we have examined the possibility that NPY and norepinephrine interact in this control. Because the stimulation of vasopressin release by the intracerebroventricular (i.c.v.) administration of norepinephrine is greater in male than in female rats, the experiments were carried out in conscious male rats and in female rats in the proestrous and non-proestrous phases of the estrous cycle. NPY (940 pmol i.c.v.) caused small sustained increases in plasma vasopressin concentrations that were greater in proestrous than in non-proestrous females and males. Norepinephrine i.c.v. increased plasma vasopressin levels transiently and to a greater extent in females than males. When NPY and norepinephrine were given together, the pattern of the vasopressin response was similar to that of norepinephrine alone. The magnitude of this response in males and proestrous females did not differ from that to norepinephrine alone; in non-proestrous females the response was twice that to norepinephrine alone. In non-proestrous rats, NPY also enhanced the pressor response to norepinephrine. Thus, NPY interacts centrally with norepinephrine in vasopressin release and cardiovascular function and this effect is dependent upon gender and phase of the estrous cycle.

Estradiol attenuates the antidiuretic action of vasopressin in ovariectomized rats.

To determine which ovarian hormone is involved in the sexually dimorphic antidiuretic action of vasopressin, the antidiuretic response to vasopressin was examined in sham-operated nonestrous female rats chronically treated with vehicle and in ovariectomized rats treated with vehicle, progesterone, estradiol, or the combination of estradiol and progesterone, respectively. Three-week-old female rats were sham operated or ovariectomized, and a slow-release hormone pellet was implanted at the 6th wk. The experiment was performed at the 10th to 12th wk in conscious, chronically instrumented rats hydrated with tap water (2% body wt). Infusion of vasopressin at rates of 10-1,000 pg.min-1.kg body wt-1 resulted in a dose-dependent antidiuretic response that was significantly enhanced in ovariectomized rats compared with the intact nonestrous females. Progesterone had no effect, whereas estradiol attenuated and restored the antidiuretic response to vasopressin to a level similar to that in intact nonestrous female rats. These results suggest that it is estrogen, but not progesterone, that reduces the antidiuretic response to vasopressin in the female rat.

Increased plasma osmolality stimulates peripheral and central vasopressin release in male and female rats.

It has been demonstrated that the neurohypophysial hormones can be released intrahypothalamically by the paraventricular (PVN) and supraoptic nuclei. The present experiments were undertaken to determine whether a physiological stimulus for vasopressin release, increased plasma osmolality, will stimulate the release of vasopressin by the PVN into the surrounding interstitial fluid, and whether the responses are affected by gender. Intravenous infusion of 2.5 M NaCl for 60 min (0.1 ml.kg-1.min-1) in conscious rats resulted in an increased vasopressin concentration in the dialysate from a microdialysis probe adjacent to the PVN. This response was greater in nonestrous females than in males. On the other hand, the rise in the plasma vasopressin concentration was greater in males than in nonestrous females. Mean arterial blood pressure increased and heart rate decreased, but these responses were not affected by gender. The role of centrally released vasopressin in the control of the peripheral release of vasopressin is conjectural, but both responses may be modulated by the gonadal steroid hormones.