Edna Peleg

Oral yohimbine increases blood pressure and sympathetic nervous outflow in hypertensive patients.

Yohimbine is an α2-adrenoceptor antagonist that is FDA approved for treatment of impotence. The drug is an indolalkylamine alkaloid chemically similar to reserpine and is believed to act through sympatholysis. We examined effects of oral yohimbine on blood pressure (BP) and plasma levels of catechols in patients with essential hypertension, a condition in which most drug treatments can produce impotence. In 25 unmedicated hypertensive subjects, vital signs were measured and blood samples were obtained through an indwelling ante-cubital venous catheter at baseline and 1 and 2 h after subjects ingested 4 5.4-mg tablets of yohimbine. Mean blood pressure (MBP) increased by an average of 5 mm Hg (p < 0.01), plasma norepinephrine (NE) levels increased by 66% (p < 0.001), and plasma dihydroxyphen-ylglycol (DHPG) levels increased by 25% (p < 0.01) at 1 h after drug administration. The magnitude of the pressor response was unrelated to baseline MBP but positively correlated with the baseline NE level (r = 0.61, p < 0.01) and with the yohimbine-induced increment in plasma NE (r = 0.4, p < 0.01). The results indicate that yohimbine does not inhibit and actually stimulates sympathetically mediated NE release in humans and that the increased NE release produces a pressor response. Yohimbine should be administered with caution to patients with high BP, especially in individuals with evidence for increased basal sympathetic outflow or those undergoing concurrent treatment with tricyclic antidepressants or other drugs that interfere with neuronal uptake or metabolism of NE.

Predominance of l-dopa in fetal plasma and the amniotic fluid during late gestation in the rat

The purpose of this study was to reevaluate catecholamine distribution in fetal and maternal compartments during late gestation in the rat. Fetal and maternal plasma and amniotic fluid were collected from anesthetized rats on consecutive days from day 17 to day 22, the day of parturition. The fluid was analyzed for dihydroxyphenylalanine (L-dopa), dopamine, norepinephrine, and epinephrine by radioenzymatic assays. Amniotic fluid volume was determined by a direct weighing method. L-Dopa concentrations constituted approximately 50% of total fetal plasma catecholamines and were significantly higher in fetal than in maternal circulation. Dopamine concentrations in fetal plasma were tenfold lower than those of L-dopa but were also significantly higher in fetal than in maternal plasma; norepinephrine levels were similar in both. Maternal plasma epinephrine levels remained relatively constant, whereas fetal epinephrine levels increased fiftyfold from day 17 to day 22. L-Dopa concentrations in the amniotic fluid were tenfold higher than those of dopamine, and the concentrations of both increased markedly during the last 2 days of gestation. However, this apparent rise could be attributed to the concomitant fivefold reduction in the amniotic fluid volume observed at this time. It is concluded that L-dopa is the predominant catecholamine in both the fetal plasma and the amniotic fluid during late gestation in the rat. At the present time, neither the source nor the possible physiologic functions of L-dopa during fetal life are known.

Reduction of thromboxane A2 synthesis in pregnancy by polyunsaturated fatty acid supplements

Objective: High-dose supplements of fish oil reduce thromboxane synthesis in nonpregnant human subjects and were therefore proposed as a means of preventing various small-vessel disorders, including preeclampsia. The effect of fish oil on thromboxane metabolism in pregnancy was investigated in our study. Study Design: Sixteen normal pregnant women in the third trimester of pregnancy were treated with Abstract daily ingestion of 6 gm fish oil capsules containing 1.6 gm of n -3 fatty acid. In five patients the treatment was stopped because of severe-flavored reflux and hiccups. Eleven patients completed 3 weeks of reatment. Twenty-four-hour urinary 11-dehydro-thromboxane B 2 was measured by means of radioimmunoassay before and after completion of the study protocol in these 11 patients and in seven ontrol pregnant women who did not receive the oil treatment. Results: A decrease ranging from 32% to 71%, in 24-hour urinary 11-dehydro-thromboxane B 2 xcretion (mean reduction from 1606 pg/mg creatinine to 779 pg/mg creatinine, p Conclusions: High-dose n -3 fatty acid intake in pregnancy significantly reduces maternal thromboxane A 2 synthesis. These results may provide a basis for a possible role of fish oil in managing patients at risk for preeclampsia.

[14] Optimization of culture conditions for short-term pituitary cell culture

Publisher Summary This chapter discusses the conditions for studying the regulation of luteinizing hormone (LH) and prolactin (PRL) secretion by releasing-inhibiting hormones. The chapter illustrates the simultaneous determination of the dose-response characteristics of dopamine (DA) inhibition of PRL secretion (lower panel, left side), LH-releasing hormone (RH) stimulation of LH secretion (upper panel, left side), and the profile of the release of these hormones following incubation with hypothalamic extracts (right side, lower and upper panels). The use of cultured pituitary cells under optimal conditions provide a powerful tool for differentiating between hypothalamic and pituitary sites of hormone action, for probing the interactions between hypothalamic and peripheral hormones at the level of the pituitary, for studying receptor parameters, and for elucidating the mechanism of hormone action at the cellular level.

Stress reaction to intense sound exposure under different arousal levels in guinea pigs

The general impact of high intensity sound exposure on 25 guinea pigs was investigated at three different levels of arousal: 10 during general anaesthesia. 10 during partial arousal, and 5 during complete arousal. Parameters recorded before and during noise exposure were mean arterial blood pressure, pulse rate, and plasma norepinephrine levels. The anaesthetized group showed no increase in the three parameters during sound exposure. Under partial arousal, pulse rate and norepinephrine level increased significantly: pulse rate from 224.5 beats/min before exposure to 278.6 beats/min during exposure, and norepinephrine level from 558 pg/ml before sound exposure to 1276 pg/ml during exposure. At the time of the complete arousal state norepinephrine and pulse rates increased significantly during noise exposure, while blood pressure showed no additional increase as a result of sound exposure.

Effect of Treatment With Lercanidipine on Heart of Cohen-Rosenthal Diabetic Hypertensive Rats

Abstract— The influence of treatment with the dihydropyridine‐type Ca2+ antagonist lercanidipine on heart and coronary microanatomic changes was investigated in spontaneously hypertensive rats, Cohen‐diabetic rats, and Cohen‐Rosenthal diabetic hypertensive rats. At 12 weeks of age, animals were left untreated (control groups) or were treated for 8 weeks with an oral dose of 3 mg/kg per day of lercanidipine. Wistar‐Kyoto rats were used as a normotensive reference group. In spontaneously hypertensive rats and diabetic hypertensive rats, systolic blood pressure was higher in comparison with Wistar‐Kyoto rats. Augmented pressure values were decreased by lercanidipine treatment. Systolic blood pressure was slightly higher in Cohen‐diabetic rats than in Wistar‐Kyoto rats, and this increase was countered by treatment with lercanidipine. In spontaneously hypertensive rats, diabetic rats, and diabetic hypertensive rats, the thickness of left ventricle and cardiocyte area were increased. Focal connective tissue areas and diffuse accumulation of connective tissue were observed in the left ventricle of spontaneously hypertensive and Cohen‐diabetic rats, respectively. Pharmacological treatment countered left ventricle thickening and restored cardiocyte area values in subendocardium. An increased thickness of tunica media accompanied by luminal narrowing was found in coronary artery branches of control spontaneously hypertensive and diabetic hypertensive rats. Treatment with lercanidipine countered vascular changes primarily in small‐sized coronary arteries. These results indicate that hypertensive, diabetic, and diabetic hypertensive rats undergo cardiac hypertrophy and vascular changes affecting small‐sized coronary arteries. Treatment with lercanidipine countered hypertension‐related cardiac and coronary changes, suggesting that this dihydropyridine‐type Ca2+ antagonist may improve heart and coronary structure in diabetes associated with hypertension.

Effect of non-drug interventions on arterial properties determined from 24-h ambulatory blood pressure measurements

Measures derived from the slope of the linear relationship between systolic and diastolic pressures obtained by 24-h ambulatory blood pressure (ABP) measurements incorporate clinical and prognostic information, and are believed to be vascular markers. Using post hoc analysis, we investigated potential changes of these ‘slope-related measures’ in three different studies conducted in hypertensive patients with before and after 24-h ABP measurements, and also evaluated the sensitivity of the results to the analysis method. Two interventional studies included 8-week device-guided breathing (DGB) exercised by 13 patients with uncontrolled blood pressure (BP), and a 6-month mineral potassium chloride-enriched diet administered to 20 elderly patients. One study was observational and involved winter-to-summer change experienced by 13 patients with controlled BP. Slope-related measures included systolic-on-diastolic slope and its equivalent 1–(diastolic-on-systolic slope) called Ambulatory Arterial Stiffness Index, and were determined using three different BP-averaging methods and two types of regression procedures. Results demonstrated sensitivity of slope-related measures to the analysis method, the most significant changes were found when the before and after 24-h ABP profiles included hourly averaged BP further averaged over the patient population, and slope-related measures were determined using symmetric (and not standard) regression. DGB was found to reduce significantly all these measures. The changes in the slope-related variables for individual patients correlated negatively with its baseline value and positively with the observed pulse pressure changes. In conclusion, the study provides evidence that DGB can affect positively vascular markers associated with cardiovascular risk, and suggests improved analysis methods for the determination of slope-related measures in interventional studies.

The correlation between isolated interventricular septal hypertrophy and 24-h ambulatory blood pressure monitoring in apparently healthy air crew

BackgroundInterventricular septal (IVS) hypertrophy is considered to affect prognosis in hypertensive patients. However, the natural history of isolated septal hypertrophy, identified by echocardiography in otherwise healthy subjects is not well defined. MethodsThe study population included 51 apparently healthy pilots with septal hypertrophy (septal thickness >u200911u2009mm) defined by routine echocardiography, with a calculated normal left ventricular (LV) mass. All pilots underwent casual blood pressure (BP) measurements and a 24-h ambulatory BP monitoring (ABPM). Hypertension (HTN) was defined as a casual measurement of >u2009140/90u2009mmHg. ResultsThe mean age of the pilots was 38u2009u2009±u2009u200911 years and the body mass index (BMI) 26.3u2009kg/m2. The 17 pilots found to be hypertensive had a higher septal thickness than the 34 counterparts with normal BP measurements (13.8u2009u2009±u2009u20092.0u2009mm versus 12.6u2009u2009±u2009u20091.7u2009mm, P u2009<u20090.04, respectively). The mean ambulatory daytime systolic and diastolic BP were higher in comparison to non-hypertensive pilots (142u2009u2009±u2009u20096.2 versus 128u2009u2009±u2009u20095.0u2009mmHg, P u2009<u20090.0001 for systolic BP and 91u2009u2009±u2009u20095.3 versus 78u2009u2009±u2009u20094.1u2009mmHg, P u2009=u20090.001 for diastolic BP), respectively. The adjusted relative risk (RR) of a subject with an IVS thickness >u200912u2009mm to be hypertensive by ABPM was 3.12 (95% confidence interval 1.04–9.37, P u2009<u20090.02). ConclusionsIsolated IVS hypertrophy, even in the presence of normal LV mass is associated with HTN. Screening healthy subjects at risk for hypertension by echocardiography enables one to identify those who should be closely monitored, using among others, ABPM.

THE RELATIONSHIP BETWEEN ENDOTHELIN AND BLOOD PRESSURE IN PREGNANT RATS

Objective: The role of endothelin in the maintenance and regulation of hypertension in spontaneously hypertensive and Wistar Kyoto rats is controversial. In view of the meager data on pregnant rats, endothelin levels and blood pressure were examined before and during pregnancy in these two strains of rats.Methods: Endothelin levels were determined with a 125I ET radioimmunoassay (RIA) kit. Systolic blood pressure was measured in conscious animals by an indirect tail cuff method using an electrosphygmomanometer and pneumatic pulse transducer (Narco Biosystems, Inc., Houston, TX). The mean of 3 measurements was recorded as a representative blood pressure for each rat.Results: The decrease in blood pressure in the spontaneously hypertensive rats (SHR) during pregnancy was very impressive, and the endothelin level also fell significantly. There was no change in endothelin level in Wistar Kyoto rats (WKY) and the fall in blood pressure was also less pronounced.Conclusions: These data indicate a mutual relation...

Saccharin Increases Fasting Blood Glucose but Not Liver Insulin Resistance in Comparison to a High Fructose-Fed Rat Model

Recent data indicate that artificial sweeteners (AS) may have deleterious effects on glucose metabolism. The purpose of this study was to compare the effects of AS and the effects of a high fructose diet (HFrD) on glucose metabolism and insulin resistance (IR) in Sprague-Dawley (SD) rats. SD rats were fed either regular chow, chow with saccharin (Sac) (0.1 mg/mL) placed in their water, or HFrD for seven weeks. Glucose, insulin, and triglycerides (Tg) levels were measured upon completion. A homeostatic model assessment (HOMA)-IR index was used to determine insulin resistance. The liver was stained to detect signs of a fatty liver. Hepatic mRNA expression of glucose metabolism regulation genes, Srepb-1c (sterol regulatory element binding protein) and ChREB (α & β) (carbohydrate response element binding protein), as well as other glycolytic and lipogenic genes including glucose-6-phosphatase (G6pc), were considered IR markers. Both HFrD and Sac significantly increased fasting blood glucose levels compare to the control (140 ± 5 and 137 ± 6 vs. 118 ± 3 mg/dL, respectively, p < 0.05). However, only HFrD increased insulin secretion (0.99 ± 0.12 vs. 0.7 ± 0.1 and 0.6 ± 0.1 ug/L), Tg levels (420 ± 43 vs. 152 ± 20 and 127 ± 13 mg/dL), and the HOMA-IR index (3.4 ± 0.4 vs. 2.3 ± 0.36 and 2.13 ± 0.3) (HFrD vs. control and sac, p < 0.05). Fatty liver changes were only observed in HFrD fed rats. The expression of ChREB β, Srepb-1c, and G6pc mRNA were only significantly elevated (between 2–10 times folds, p < 0.05) in HFrD fed rats. Sac may increase fasting blood glucose but has no effect on liver insulin resistance.