Abstract-Men are at greater risk for cardiovascular and renal disease than are age-matched, premenopausal women.Recent studies using the technique of 24-hour ambulatory blood pressure monitoring have shown that blood pressure is higher in men than in women at similar ages. After menopause, however, blood pressure increases in women to levels even higher than in men. Hormone replacement therapy in most cases does not significantly reduce blood pressure in postmenopausal women, suggesting that the loss of estrogens may not be the only component involved in the higher blood pressure in women after menopause. In contrast, androgens may decrease only slightly, if at all, in postmenopausal women. In this review the possible mechanisms by which androgens may increase blood pressure are discussed. Findings in animal studies show that there is a blunting of the pressure-natriuresis relationship in male spontaneously hypertensive rats and in ovariectomized female spontaneously hypertensive rats treated chronically with testosterone. The key factor in controlling the pressure-natriuresis relationship is the renin-angiotensin system (RAS). The possibility that androgens increase blood pressure via the RAS is explored, and the possibility that the RAS also promotes oxidative stress leading to production of vasoconstrictor substances and reduction in nitric oxide availability is proposed. Key Words: sex characteristics Ⅲ hypertension Ⅲ angiotensin II Ⅲ nitric oxide Ⅲ oxidative stress I n this review gender differences in blood pressure control are explored, including possible mechanisms by which androgens may increase blood pressure. Gender Differences in Blood Pressure Regulation in HumansMen are generally at greater risk for cardiovascular and renal disease than are age-matched, premenopausal women. Recent studies using the technique of 24-hour ambulatory blood pressure monitoring have shown that blood pressure is higher in men than in women at similar ages. As shown in Figure 1, Wiinber and colleagues 1 studied 352 normotensive (for age) Danish men and women, aged 20 to 79 years, and found that blood pressure increased with aging in both men and women, but that men had higher 24-hour mean blood pressure, by approximately 6 to 10 mm Hg, than did women, until the age of 70 to 79 years, when blood pressure was similar for men and women. Khoury and colleagues 2 performed ambulatory blood pressure monitoring on 131 men and women, aged 50 to 60 years, and found that men had higher blood pressure than did women. Findings were similar in a meta-analysis study performed by Staessen et al. 3 In addition, the Third National Health and Nutrition Evaluation Survey (NHANES III) showed that, in general, men had higher blood pressure than women through middle age. 4 Furthermore, the incidence of uncontrolled hypertension is also greater in men than in women. 5After menopause, however, blood pressure increases in women as well. The data from NHANES III, shown in Figure 2, confirmed that by 60 to 69 years of age, non-Hispanic black and Hi...

Abstract-A reduction in nitric oxide (NO) synthesis has been suggested to play a role in pregnancy-induced hypertension.We have recently reported that normal pregnancy in the rat is associated with significant increases in whole-body NO production and renal protein expression of neuronal and inducible NO synthase. The purpose of this study was to determine whether whole-body and renal NO production is reduced in a rat model of pregnancy-induced hypertension produced by chronically reducing uterine perfusion pressure starting at day 14 of gestation. Chronic reductions in uterine perfusion pressure resulted in increases in arterial pressure of 20 to 25 mm Hg, decreases in renal plasma flow (Ͻ23%) and glomerular filtration rate (Ͻ40%), but no difference in urinary nitrite/nitrate excretion relative to control pregnant rats. In contrast, reductions in uterine perfusion pressure in virgin rats resulted in no significant effects on arterial pressure. Renal endothelial (Ͻ4%) and inducible (Ͻ11%) NO synthase protein expression did not decrease significantly in the chronically reduced uterine perfusion pressure rats relative to normal pregnant rats; however, significant reductions in neuronal NO synthase were observed (Ͻ30%). The results of this study indicate that the reduction in renal hemodynamics and the increase in arterial pressure observed in response to chronic decreases in uterine perfusion pressure in pregnant rats are associated with no change in whole-body NO production and a decrease in renal protein expression of neuronal NO synthase. (Hypertension. 2000;37:1191-1195.)Key Words: preeclampsia Ⅲ hypertension, pregnancy Ⅲ glomerular filtration rate Ⅲ renal blood flow Ⅲ plasma Ⅲ endothelium Ⅲ nitric oxide P reeclampsia is a multisystemic disorder of pregnancy estimated to affect 5% to 10% of all pregnancies in the United States. 1,2 Although preeclampsia is one of the leading causes of maternal death and the main contributor of prenatal morbidity, the mechanisms responsible for this disorder are unclear. 1-3 Preeclampsia develops during pregnancy and ceases after delivery, implicating the placenta as a primary cause. 1,4 Manifestations generally associated with preeclampsia include an increased responsiveness to vasoconstrictors, increases in arterial pressure, decreases in glomerular filtration rate (GFR) and renal plasma flow (RPF), proteinuria, and vascular endothelial damage. 1,2,5 The initiating event in preeclampsia is suggested to involve reduced placental perfusion, which leads to maternal endothelial cell dysfunction. 1,3,4 The factors involved in mediating the hypertension during preeclampsia are unknown and may involve a delicate balance of vasoconstrictors and vasodilators of which nitric oxide (NO) may play an important role. 1,4,6 Evidence indicates that NO plays an important role in mediating physiological changes during normal pregnancy. 6,7 Increases in regional blood flow, RPF, and GFR during pregnancy are attenuated by systemic NO synthesis inhibition. 8,9 Urinary excretion of cGMP, a second ...

Abstract-Studieswere performed m intact male and female, gonadectomlzed male and female, and gonadectomzed female rats gwen testosterone for 5 weeks to mve$tlgate the role played by testosterone m altered blood pressure control and pressure-natrmreas m male SHR Serum testosterone levels reached a peak at 12 weeks of age m Intact male SHR Systohc blood pressure, measured weekly from 5 to 20 weeks of age, was slmllar between groups until 12 weeks of age when blood pressure became higher m males (195+3 Key Words: sexual dlmorphlsm n androgens n estrogens w blood pressure M en are at greater nsk for cardiovascular and renal disease at an earher age than are women Recent studies using the technique of 24-hour ambulatory blood pressure monltormg m normotenslve populations have shown that blood pressure 1s higher m men than m women at snnllar ages l-3 Wnnberg et al' studied 352 Danish men and women, aged 20 to 79 years, who were divided into groups by sex and age Blood pressure increased with aging m both men and women, but the men had higher 24-hour mean blood pressures than did the women for all age groups except the 70-to 79-year-old mdlvlduals m whom blood pressures were numerically hlghel In the men but statlstlcally similar for men and women ' Staessen et al' performed meta-analysis using all ambulatory blood pressure data reported m English or French between 1980 and 1989 m men and women aged 13 to 50 years They also found that 24-hour systolic and dlastohc blood pressures were higher m men than m women Anastos et al3 have also shown that the incidence of uncontrolled hypertension IS greater In men than m women Thus, epldemlologlcai studies indicate that men have higher blood pressures than do women The mechanisms for the sex difference m blood pressure regulation In humans are unknownThe sex-associated differences m blood precsure regulation observed m humans have also been documented m various ammal models For example, male SHR have higher blood pressures than do females of similar ages '-' Crofton et al' and Rowland and Fregly" found that arterial pressure in male Dahl salt-sensitive rat? increased more rapidly on a high-fodlum chloride diet than m females Two other models m the rat m which hypertension progresses more rapidly m males are the deoxycortlcosterone-salt model of hypertension"' and the New Zealand genetically hypertensive rat "Although hlghel blood pressure has been documented In men, the mechamsms responsible for the sex difference have yet to be determined Some studies have lmphed that androgens may play an important role m the progression of cardlovascular diseases For example, several studies have shown that elevations m blood pressure are attenuated by gonadectomy of the males m animal models of hypertension, such as SHR and Dahl salt-sensltlve rats ",') Although studies pomt to androgens as a possible mediator m the progre$slon of hypertension m male animals, the mechamsms whereby male hormones may increase blood pressure remam uncertainTo date all forms of hypertension have been found to b...

Abstract-In this review, we examine the possibility that small increments in angiotensin II are responsible for an increase in blood pressure and maintenance of hypertension through the stimulation of oxidative stress. A low dose of angiotensin II (2 to 10 ng ⅐ kg Ϫ1 ⅐ min Ϫ1 , which does not elicit an immediate pressor response), when given for 7 to 30 days by continuous intravenous infusion, can increase mean arterial pressure by 30 to 40 mm Hg. This slow pressor response to angiotensin is accompanied by the stimulation of oxidative stress, as measured by a significant increase in levels of 8-iso-prostaglandin F 2␣ (F 2 -isoprostane). Superoxide radicals and nitric oxide can combine chemically to form peroxynitrite, which can then oxidize arachidonic acid to form F 2 -isoprostanes. F 2 -isoprostanes exert potent vasoconstrictor and antinatriuretic effects. Furthermore, angiotensin II can stimulate endothelin production, which also has been shown to stimulate oxidative stress. In this way, a reduction in the concentration of nitric oxide (which is quenched by superoxide) along with the formation of F 2 -isoprostanes and endothelin could potentiate the vasoconstrictor effects of angiotensin II. We hypothesize that these mechanisms, which underlie the development of the slow pressor response to angiotensin II, also participate in the production of hypertension when circulating angiotensin II levels appear normal, as occurs in many cases of essential and renovascular hypertension.