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(Hypertension. 1998;31:435.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Testosterone Exacerbates Hypertension and Reduces Pressure-Natriuresis in Male Spontaneously Hypertensive Rats

Jane F. Reckelhoff; Huimin Zhang; Joey P. Granger

From the Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, Miss.

Correspondence to Jane F. Reckelhoff, PhD, Department of Physiology and Biophysics, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216-4505. E-mail: jfr{at}fiona.umsmed.edu

	Abstract

Top Abstract Introduction Methods Results Discussion References

 
Studies were performed in intact male and female, gonadectomized male and female, and gonadectomized female rats given testosterone for 5 weeks to investigate the role played by testosterone in altered blood pressure control and pressure-natriuresis in male SHR. Serum testosterone levels reached a peak at 12 weeks of age in intact male SHR. Systolic blood pressure, measured weekly from 5 to 20 weeks of age, was similar between groups until 12 weeks of age when blood pressure became higher in males (195±3 mm Hg) than in females (168±3 mm Hg) or males castrated at 4 weeks (173±4 mm Hg). At 17 to 19 weeks direct measurement of arterial pressure in anesthetized rats confirmed that mean arterial pressure was higher in male (182±1 mm Hg) than in female (159±2 mm Hg) and castrated male SHR (159±2 mm Hg). In addition, testosterone (5 mg in Silastic pellets, SC for 5 weeks) administered to ovariectomized (ovx+T) females caused arterial pressure to increase by mm11% (175±2 mm Hg), which was significantly higher than in intact female, castrated male, or untreated ovariectomized (ovx) female SHR (158±2 mm Hg). Acute pressure-natriuresis was blunted in male SHR compared with females, castrated males, or ovx females, in which this relationship was similar. Pressure-natriuresis was also blunted in ovx+T females as found in intact male SHR. These data support the hypothesis that male sex hormones contribute to the exacerbation of hypertension in SHR by reducing pressure-natriuresis.

Key Words: sexual dimorphism • androgens • estrogens • blood pressure

Abbreviations: GFR = glomerular filtration rate • ovx = ovariectomized • ovx+T = ovariectomized females that received testosterone for 5 weeks • RPF = renal plasma flow • SHR = spontaneously hypertensive rat(s)

	Introduction

Top Abstract Introduction Methods Results Discussion References

 
Men are at greater risk for cardiovascular and renal disease at an earlier age than are women. Recent studies using the technique of 24-hour ambulatory blood pressure monitoring in normotensive populations have shown that blood pressure is higher in men than in women at similar ages.^1–3 Wiinberg et al¹ 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 in 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 individuals in whom blood pressures were numerically higher in the men but statistically similar for men and women.¹ Staessen et al² performed meta-analysis using all ambulatory blood pressure data reported in English or French between 1980 and 1989 in men and women aged 13 to 50 years. They also found that 24-hour systolic and diastolic blood pressures were higher in men than in women. Anastos et al³ have also shown that the incidence of uncontrolled hypertension is greater in men than in women. Thus, epidemiological studies indicate that men have higher blood pressures than do women. The mechanisms for the sex difference in blood pressure regulation in humans are unknown.

The sex-associated differences in blood pressure regulation observed in humans have also been documented in various animal models. For example, male SHR have higher blood pressures than do females of similar ages.^4–7 Crofton et al⁸ and Rowland and Fregly⁹ found that arterial pressure in male Dahl salt-sensitive rats increased more rapidly on a high-sodium chloride diet than in females. Two other models in the rat in which hypertension progresses more rapidly in males are the deoxycorticosterone-salt model of hypertension¹⁰ and the New Zealand genetically hypertensive rat.¹¹

Although higher blood pressure has been documented in men, the mechanisms responsible for the sex difference have yet to be determined. Some studies have implied that androgens may play an important role in the progression of cardiovascular diseases. For example, several studies have shown that elevations in blood pressure are attenuated by gonadectomy of the males in animal models of hypertension, such as SHR and Dahl salt-sensitive rats.^8,9 Although studies point to androgens as a possible mediator in the progression of hypertension in male animals, the mechanisms whereby male hormones may increase blood pressure remain uncertain.

To date all forms of hypertension have been found to be associated with a reduction in the pressure-natriuresis relationship.¹² Previous studies by other investigators have documented a shift in the pressure-natriuresis relationship in SHR.^13,14 If androgens in fact contribute to the exaggerated rise in blood pressure in male SHR, then they also should have an effect on the pressure-natriuresis relationship. The present study, therefore, was designed to test this hypothesis by measuring the testosterone-mediated component of pressure-natriuresis in the male SHR.

	Methods

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Rats
All studies were performed using male and female SHR, purchased from Harlan Sprague-Dawley. Male and female SHR at 3 weeks of age were castrated or ovx by the vendor and received at 4 weeks of age. Rats were maintained on standard rat diet (Teklad; Harlan Sprague-Dawley) in a 12-hour:12-hour light/dark cycle. All studies were approved by the Animal Care and Use Committee, University of Mississippi Medical Center, using National Institutes of Health Guidelines.

Serial Conscious Blood Pressure Measurements
Starting at 5 weeks of age blood pressure was measured weekly for 7 weeks in intact male, female, and castrated male SHR (n=16 each sex) by tail plethysmography (IITC, Inc).

Testosterone Treatment of ovx Female SHR and Serum Testosterone Assays
After arrival at 4 weeks of age, ovx female SHR were allowed to mature to 12 to 13 weeks of age and were then implanted subcutaneously in the shoulder area with 0.19-mm Silastic pellets (0.062 in ID, 0.125 in OD; Dow Corning) containing 5 mg of testosterone.¹⁵ After 3 weeks the pellets were replaced.

Serum testosterone was measured at the time of renal function studies in ovx females treated with testosterone and in anesthetized intact male SHR at 2-week intervals as they matured from 6 to 14 weeks of age (n=5 per age group), using a commercially available radioimmunoassay kit (Coat-A-Count Total Testosterone Assay kit, Diagnostic Products Corporation).

Renal Function and Acute Pressure-Natriuresis Studies
At 17 to 19 weeks of age, male (n=9), female (n=7), castrated male (n=8), ovx female (n=9), and ovx+T females (n=7) were anesthetized by intraperitoneal injection of the thiobarbiturate, Inactin (100 to 110 mg/kg body weight; A. Lockwood) and placed on a temperature-regulated surgery table to maintain rectal temperature at 36 to 38°C. Catheters were placed in the femoral artery (for continuous monitoring of blood pressure and for blood sampling) and in the femoral vein for infusion of isoncotic artificial rat plasma (2.5 g/dL bovine immunoglobulin, 2.5 g/dL bovine serum albumin in Ringer’s solution) at 12.5 mL/kg per hour for 45 minutes during the preparatory surgery and thereafter at 1.5 mL/kg per hour throughout the experimental period to maintain an euvolemic preparation.^16,17 A catheter was placed in the left jugular vein for infusion of 0.9% saline with [¹²⁵I]iodoiothalamate (Glofil 0.05 µCi/kg/min; Cypros) and [¹³¹I]iodohippuran (0.1 µCi/kg/min; Syncor International) at 1 to 2 mL/h (depending on body weight). A tracheostomy was performed. A midline abdominal incision was then made, and catheters were placed in both ureters for collection of urine samples into weighed microfuge tubes.

After a 50-minute equilibration for isotope infusion and at the ambient blood pressure of the rat, a timed (15 to 30 minutes) urine sample and a midpoint arterial blood sample were collected. After this period, a snare was placed around the aorta above the renal arteries, and the snare was tightened in a stepwise fashion to produce graded decreases in renal perfusion pressure of approximately 20 mm Hg down to 110±5 mm Hg. Each decrease in blood pressure was followed by a 10-minute equilibration period and a 15- to 30-minute period during which urine and midpoint blood samples were again taken. After the experiment the kidneys were removed and weighed.

Analytical Methods
Samples of urine (25 to 50 µL) and femoral arterial plasma (50 µL) were counted by gamma counter (Searle, Tm Analytic). Urinary and plasma sodium were measured by atomic absorption (Instrumentation Laboratory).

Calculations
These measurements allowed for the calculation of GFR, RPF, renal vascular resistance,¹⁸ and urinary sodium excretion.

Statistical Analyses
The data were analyzed by ANOVA for repeated measures within groups, using Statview 512 software for the Macintosh. Significance was defined as P<.05. All data values are expressed as mean±SEM.

	Results

Top Abstract Introduction Methods Results Discussion References

 
As shown in Fig 1A, blood pressure as measured by tail plethysmography, increased with maturity in all SHR. However, at 12 weeks of age and thereafter, blood pressures in male SHR were significantly higher than in females. Castration prevented the blood pressure from increasing in males so that the blood pressure was the same as in females.

View larger version (18K): [in this window] [in a new window]   Figure 1. Systolic blood pressure in male, female, and castrated male SHR with increasing age (A) and serum testosterone in male SHR (B). A, Blood pressure was measured in conscious rats by tail plethysmography. *P<.05, compared with female or castrated male SHR. B, Serum testosterone levels in male SHR. P<.05, compared with value at 6 weeks of age.

Testosterone levels (Fig 1B) in intact male SHR were below detectable limits at 6 weeks of age but started to increase by 8 weeks and reached a peak at 12 weeks of age. This coincides with the time when blood pressures in male SHR became significantly higher than in females or castrated males.

As shown in the Table and Fig 2, in anesthetized rats, as in conscious animals, mean arterial pressure at 17 to 19 weeks of age was higher in intact males than in females. Castrated males had blood pressures similar to females, whereas testosterone treatment of ovariectomized female SHR for 5 weeks resulted in a significant increase in arterial pressure. Serum testosterone levels in ovx+T females at the time of the experiment were similar to values in intact male SHR at 9 to 10 weeks of age (16±6 ng/mL). Ovariectomy alone had no effect on mean arterial pressure in female SHR.

View this table: [in this window] [in a new window]   Body Weight, Kidney Weight, and Hemodynamics in SHR at Ambient Blood Pressure

View larger version (20K): [in this window] [in a new window]   Figure 2. Sex differences and the role of androgens in mean arterial blood pressure in SHR. Ambient blood pressures were measured at 17 to 19 weeks of age via femoral catheter in male, female, castrated male, ovx female, and ovx+T female SHR. *P<.05, compared with intact male; ,, P<.05 compared with female, castrated male, and ovx female SHR, respectively.

GFR and RPF, when factored for kidney weight, were similar in all groups of rats at ambient blood pressure (shown in the Table). In addition, GFR and RPF were similar in all groups at the reduced renal perfusion pressures.

As shown in Fig 3, there was a hypertensive shift in the acute pressure-natriuresis relationship in male SHR when compared with females. Castration of the male shifted the pressure-natriuresis relationship back to values found in intact females. Moreover, ovariectomized female SHR treated with testosterone had a blunted pressure-natriuresis that was not dissimilar from intact male SHR. Ovariectomy alone had no effect on pressure-natriuresis.

View larger version (22K): [in this window] [in a new window]   Figure 3. Acute pressure-natriuresis relationships in anesthetized SHR. Acute pressure-natriuresis studies were conducted in anesthetized intact male , intact female , castrated male , ovx female , and ovx+T female SHR, aged 17 to 19 weeks, as described in "Methods." *P<.05, compared with male SHR at comparable renal perfusion pressure.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
The major findings of the present study are that androgens mediate the exaggerated blood pressure and hypertensive shift in the pressure-natriuresis relationship in male SHR.

During maturation, we found that blood pressure increases in all SHR but becomes significantly higher in males than females at 12 weeks of age. In addition we report that castration of males reduces blood pressure to levels that were not different from blood pressures in females. Our data are consistent with previous studies by Masubuchi et al⁵ who also documented that female SHR had lower blood pressures than males and that castration attenuated the hypertension in males. The present study extends these findings by demonstrating that the exacerbation of the hypertension in the male SHR occurs at a time when serum testosterone levels have reached a peak at 12 weeks of age. We also found that androgens play a role in mediating the exacerbation of hypertension in male SHR, since 5 weeks of treatment with testosterone increased blood pressure in ovariectomized female SHR by 10% when compared with intact or ovariectomized females or castrated males. In fact, these blood pressure levels were only 4% lower than in intact males.

Several lines of evidence indicate that there are sex differences in blood pressure regulation in humans. In addition to the studies showing sex differences in blood pressure with aging in adults,^1,2 Bachmann et al¹⁹ documented that blood pressure in a German population of children, aged 4 to 18 years, increased with age in both boys and girls, but the increase was significantly steeper during adolescence in males than in the preadolescent period. Harschfield et al²⁰ made similar findings in a population of American children, aged 10 to 18 years. These investigators also found that blood pressures were higher in boys than girls in all age groups while awake and was higher in male adolescents, aged 16 to 18, while asleep, a time when testosterone levels are highest. These studies suggest that androgens may play a role in mediating the increase in blood pressure with puberty in male adolescents.

Although studies have implicated androgens such as testosterone in the progression of hypertension, the mechanism(s) by which androgens could affect blood pressure are unknown. The kidney has long been known to play an important role in mediating the hypertension of SHR. Cross-transplantation studies have shown that transplantation of the SHR kidney into normotensive F1 hybrids of SHR and Wistar rats resulted in hypertension in the F1 rats.^21,22 Conversely, the hypertension was attenuated in SHR when they were transplanted with a kidney from the normotensive Wistar or the F1 hybrid.^21,22 Furthermore, independent studies by Khraibi and Knox¹³ and Roman¹⁴ have shown that there are alterations in the renal pressure-natriuresis relationship in SHR as found in all other models of hypertension.¹² Whether sex differences in blood pressure regulation are also associated with alterations in pressure-natriuresis, however, has not been shown previously. Indeed we found that intact male SHR excrete a lower level of sodium at equivalent blood pressures than do females or castrated male SHR. Moreover, testosterone treatment of ovx female SHR also resulted in a hypertensive shift in the pressure-natriuresis relationship, and this suggests that it is specifically testosterone, or a metabolite, that plays a role in the blunted pressure-natriuresis relationship in male SHR compared with female SHR.

Although we showed in the present study that androgens cause a blunting in the pressure-natriuresis relationship in SHR, our studies do not address the exact mechanism(s) by which androgens may mediate this change. Testosterone or its metabolites, mediated via androgen receptors, could have a direct effect on tubular reabsorption of sodium and thereby cause a shift in the pressure-natriuresis relationship. We have preliminary data that androgen receptors are located in nuclei of renal proximal tubule cells.²³ Alternatively, testosterone could affect pressure-natriuresis by indirect mechanisms such as activation of the renin-angiotensin system. Plasma renin activity has been shown to be higher in men than in women.²⁴ Furthermore, male rats have higher angiotensinogen levels than females, and testosterone treatment increases and castration decreases angiotensinogen mRNA and plasma renin.^25,26 Future studies will be necessary to determine the mechanism(s) by which androgens shift the pressure-natriuresis relationship and increase blood pressure in SHR.

Sex differences in blood pressure have been suggested to be due to protection of the female by estrogens. To determine the role that estrogens may play in the progression of hypertension in female SHR, we compared blood pressure in intact and ovariectomized female SHR. There was no difference in the mean arterial pressures between the two groups. Furthermore, ovariectomy did not affect renal pressure-natriuresis. These data indicate that the presence of female hormones such as estrogen are not responsible for attenuating the hypertension and causing protection in the female SHR.

In summary, blood pressure in male SHR becomes significantly higher than in females at 12 weeks of age, a time when serum testosterone levels in the male reach their peak. Castration of the male SHR attenuated the increase in blood pressure. Moreover, testosterone treatment of ovariectomized female SHR results in increases in blood pressure as found in intact male SHR. These data implicate androgens in mediating the progression of hypertension in the male. The pressure-natriuresis relationship is also blunted in the male SHR compared with female or castrated male SHR. Furthermore, testosterone treatment of ovariectomized female SHR results in blunting of the pressure-natriuresis relationship as found in intact male SHR. These data support the hypothesis that male sex hormones contribute to the exacerbation of hypertension in the male SHR by reducing pressure-natriuresis.

	Acknowledgments

 
This work was supported by funds from National Institutes of Health (Grants HL 51971 and HL 38499) and American Heart Association, Mississippi Affiliate (Grant 9307720S).

Received September 7, 1997; first decision October 15, 1997; accepted October 24, 1997.

	References

Top Abstract Introduction Methods Results Discussion References

 
1. Wiinberg N, Hoegholm A, Christensen HR, Bang LE, Mikkelsen KL, Nielsen PE, Svendsen TL, Kampmann JP, Madsen NH, Bentzon MW. 24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender. Am J Hypertens. 1995; 8 : 978 –986.[Medline] [Order article via Infotrieve]

2. Staessen J, Fagard R, Lijnen P, Thijs L, Van Hoof R, Amery A. Reference values for ambulatory blood pressure: a meta-analysis. J Hypertens. 1990; 8 (suppl 6): S57 –S64.

3. Anastos K, Charney P, Cohen E, Jones CY, Marte C, Swiderski DM, Wheat ME, Williams S. Hypertension in women: what is really known? The Women’s Caucus, Working Group on Women’s Health of the Society of General Internal Medicine. Ann Intern Med. 1991; 115 : 287 –293.[Abstract/Free Full Text]

4. Ganten U, Schroder G, Witt M, Zimmerman F, Ganten D, Stock G. Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment. J Hypertens. 1989; 7 : 721 –726.[Medline] [Order article via Infotrieve]

5. Masubuchi Y, Kumai T, Uematsu A, Komoriyama K, Hirai M. Gonadectomy-induced reduction in blood pressure in adult spontaneously hypertensive rats. Acta Endocrinol (Copenh). 1982; 101 : 154 –160.[Medline] [Order article via Infotrieve]

6. Iams SG, McMurtry JP, Wexler BC. Aldosterone, deoxycorticosterone, and prolactin changes during lifespan of chronically and spontaneously hypertensive rats. Endocrinology 1979; 104 : 1357 –2363.[Abstract/Free Full Text]

7. Chen Y-F, Meng Q-M. Sexual dimorphism of blood pressure in spontaneously hypertensive rats is androgen dependent. Life Sci. 1991; 48 : 85 –96.[Medline] [Order article via Infotrieve]

8. Crofton JT, Ota M, Share L. Role of vasopressin, the renin-angiotensin system, and sex in Dahl salt-sensitive hypertension. J Hypertens. 1993; 11 : 1031 –1038.[Medline] [Order article via Infotrieve]

9. Rowland NE, Fregly MJ. Role of gonadal hormones in hypertension in the Dahl salt-sensitive rat. Clin Exp Hypertens. 1992; A14 : 367 –375.

10. Ouchi Y, Share L, Crofton JT, Iitake K, Brooks DP. Sex difference in the development of deoxycorticosterone-salt hypertension in the rat. Hypertension. 1987; 9 : 172 –177.[Abstract/Free Full Text]

11. Ashton N, Balment RJ. Sexual dimorphism in renal function and hormonal status of New Zealand genetically hypertensive rats. Acta Endocrinol (Copenh). 1991; 124 : 91 –97.

12. Guyton AC, Coleman TG, Cowley AW Jr, Scheel KW, Manning RD, Norman RA. Arterial pressure regulation: overriding dominance of the kidneys in long-term regulation and in hypertension. Am J Med. 1972; 52 : 584 –594.[Medline] [Order article via Infotrieve]

13. Khraibi AA, Knox FG. Effect of acute renal decapsulation on pressure natriuresis in SHR and WKY rats. Am J Physiol. 1989; 257 : F785 –F789.[Medline] [Order article via Infotrieve]

14. Roman RJ. Altered pressure-natriuresis relationship in young spontaneously hypertensive rats. Hypertension. 1987; 9 (suppl III): III-130 -III-136.[Medline] [Order article via Infotrieve]

15. Jenkins C, Salisbury R, Ely D. Castration lowers and testosterone restores blood pressure in several rat strains on high sodium diets. Clin Exp Hypertens. 1994; 16 : 611 –625.[Medline] [Order article via Infotrieve]

16. Ichikawa I, Maddox DA, Cogan MG, Brenner BM. Dynamics of glomerular ultrafiltration in euvolemic Munich Wistar rats. Renal Physiol. 1978; 1 : 121 –131.

17. Reckelhoff JF, Manning RD Jr. Role of endothelial-derived nitric oxide in the control of the renal microvasculature in aging male rats. Am J Physiol. 1993; 265 : R1126 –R1131.[Medline] [Order article via Infotrieve]

18. Reckelhoff JF. Age-related changes in renal hemodynamics in female rats: role of multiple pregnancy and NO. Am J Physiol. 1997; 272 : R1985 –R1989.[Medline] [Order article via Infotrieve]

19. Bachmann H, Horacek U, Leowsky M, Hirche H. Blood pressure in children and adolescents aged 4 to 18: correlation of blood pressure values with age, sex, body height, body weight, and skinfold thickness. Monatsschr Kinderheild. 1987; 135 : 128 –134.

20. Harshfield GA, Alpert BS, Pulliam DA, Somes GW, Wilson DK. Ambulatory blood pressure recordings in children and adolescents. Pediatrics. 1994; 94 : 180 –184.[Abstract/Free Full Text]

21. Kawabe K, Watanabe TX, Shiono K, Sokabe H. Influence on blood pressure of renal isografts between SHR and normotensive rats, utilizing F1 hybrids. Jpn Heart J. 1978; 19 : 886 –894.[Medline] [Order article via Infotrieve]

22. Rettig R, Folberth CG, Graf C, Kopf D, Stauss H, Unger T. Are renal mechanisms involved in primary hypertension? Evidence from kidney transplantation studies in rats. Klin Wochenschr. 1991; 69 : 597 –602.[Medline] [Order article via Infotrieve]

23. Hennington BS, Henegar L, Sinning AR, Granger JP, Reckelhoff JF. Localization of androgen receptors in the kidney of male rats. Hypertension. 1997; 30 : 510 . Abstract.

24. James GD, Sealey JE, Muller F, Alderman M, Madhavan S, Laragh JH. Renin relationship to sex, race and age in normotensive population. J Hypertens. 1986; 4 (suppl 5): S387 –S389.

25. Ellison KE, Ingelfinger JR, Pivor M, Dzau VJ. Androgen regulation of rat renal angiotensinogen messenger RNA expression. J Clin Invest. 1989; 83 : 1941 –1945.[Medline] [Order article via Infotrieve]

26. Chen Y-F, Naftilan AJ, Oparil S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension. 1992; 19 : 456 –463.[Abstract/Free Full Text]

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				D. Song, E. Arikawa, D. Galipeau, M. Battell, and J. H. McNeill Androgens Are Necessary for the Development of Fructose-Induced Hypertension Hypertension, March 1, 2004; 43(3): 667 - 672. [Abstract] [Full Text] [PDF]

				F. J. Charchar, M. Tomaszewski, B. Lacka, J. Zakrzewski, E. Zukowska-Szczechowska, W. Grzeszczak, and A. F. Dominiczak Association of the Human Y Chromosome with Cholesterol Levels in the General Population Arterioscler Thromb Vasc Biol, February 1, 2004; 24(2): 308 - 312. [Abstract] [Full Text]

				L. A. Fortepiani, L. Yanes, H. Zhang, L. C. Racusen, and J. F. Reckelhoff Role of Androgens in Mediating Renal Injury in Aging SHR Hypertension, November 1, 2003; 42(5): 952 - 955. [Abstract] [Full Text] [PDF]

				M. Quinkler, C. Bumke-Vogt, B. Meyer, V. Bahr, W. Oelkers, and S. Diederich The Human Kidney Is a Progesterone-Metabolizing and Androgen-Producing Organ J. Clin. Endocrinol. Metab., June 1, 2003; 88(6): 2803 - 2809. [Abstract] [Full Text] [PDF]

				J Song, I Narita, S Goto, N Saito, K Omori, F Sato, J Ajiro, D Saga, D Kondo, M Sakatsume, et al. Gender specific association of aldosterone synthase gene polymorphism with renal survival in patients with IgA nephropathy J. Med. Genet., May 1, 2003; 40(5): 372 - 376. [Full Text] [PDF]

				M. A. Cavasin, S. S. Sankey, A.-L. Yu, S. Menon, and X.-P. Yang Estrogen and testosterone have opposing effects on chronic cardiac remodeling and function in mice with myocardial infarction Am J Physiol Heart Circ Physiol, May 1, 2003; 284(5): H1560 - H1569. [Abstract] [Full Text] [PDF]

				K. Nakagawa, J. S. Marji, M. L. Schwartzman, M. R. Waterman, and J. H. Capdevila Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R1055 - R1062. [Abstract] [Full Text] [PDF]

				L. A. Fortepiani, H. Zhang, L. Racusen, L. J. Roberts II, and J. F. Reckelhoff Characterization of an Animal Model of Postmenopausal Hypertension in Spontaneously Hypertensive Rats Hypertension, March 1, 2003; 41(3): 640 - 645. [Abstract] [Full Text] [PDF]

				O. Baltatu, C. Cayla, R. Iliescu, D. Andreev, and M. Bader Abolition of End-Organ Damage by Antiandrogen Treatment in Female Hypertensive Transgenic Rats Hypertension, March 1, 2003; 41(3): 830 - 833. [Abstract] [Full Text] [PDF]

				M. Dodic, T. Abouantoun, A. O'Connor, E. M. Wintour, and K. M. Moritz Programming Effects of Short Prenatal Exposure to Dexamethasone in Sheep Hypertension, November 1, 2002; 40(5): 729 - 734. [Abstract] [Full Text] [PDF]

				N. Tamaya-Mori, K. Uemura, and A. Iguchi Gender Differences in the Dietary Lard-Induced Increase in Blood Pressure in Rats Hypertension, May 1, 2002; 39(5): 1015 - 1020. [Abstract] [Full Text] [PDF]

				R. K. Dubey, S. Oparil, B. Imthurn, and E. K. Jackson Sex hormones and hypertension Cardiovasc Res, February 15, 2002; 53(3): 688 - 708. [Abstract] [Full Text] [PDF]

				C. K. Roberts, N. D. Vaziri, and R. J. Barnard Protective effects of estrogen on gender-specific development of diet-induced hypertension J Appl Physiol, November 1, 2001; 91(5): 2005 - 2009. [Abstract] [Full Text] [PDF]

				J. F. Reckelhoff Gender Differences in the Regulation of Blood Pressure Hypertension, May 1, 2001; 37(5): 1199 - 1208. [Abstract] [Full Text] [PDF]

				A. Caplea, D. Seachrist, G. Dunphy, and D. Ely Sodium-induced rise in blood pressure is suppressed by androgen receptor blockade Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1793 - H1801. [Abstract] [Full Text] [PDF]

				A. M. G. Verhagen, D. M. A. Attia, H. A. Koomans, and J. A. Joles Male gender increases sensitivity to proteinuria induced by mild NOS inhibition in rats: role of sex hormones Am J Physiol Renal Physiol, October 1, 2000; 279(4): F664 - F670. [Abstract] [Full Text] [PDF]

				G. G. Geary, D. N. Krause, and S. P. Duckles Gonadal hormones affect diameter of male rat cerebral arteries through endothelium-dependent mechanisms Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H610 - H618. [Abstract] [Full Text] [PDF]

				P. A. Lotufo, C. U. Chae, U. A. Ajani, C. H. Hennekens, and J. E. Manson Male Pattern Baldness and Coronary Heart Disease: The Physicians' Health Study Arch Intern Med, January 24, 2000; 160(2): 165 - 171. [Abstract] [Full Text] [PDF]

				J. F. Reckelhoff, H. Zhang, and K. Srivastava Gender Differences in Development of Hypertension in Spontaneously Hypertensive Rats : Role of the Renin-Angiotensin System Hypertension, January 1, 2000; 35(1): 480 - 483. [Abstract] [Full Text] [PDF]

				P. August Hypertension in Men J. Clin. Endocrinol. Metab., October 1, 1999; 84(10): 3451 - 3454. [Full Text] [PDF]

				J. F. Reckelhoff, H. Zhang, K. Srivastava, and J. P. Granger Gender Differences in Hypertension in Spontaneously Hypertensive Rats : Role of Androgens and Androgen Receptor Hypertension, October 1, 1999; 34(4): 920 - 923. [Abstract] [Full Text] [PDF]

				M. L Kuroski de Bold Estrogen, natriuretic peptides and the renin-angiotensin system Cardiovasc Res, March 1, 1999; 41(3): 524 - 531. [Abstract] [Full Text] [PDF]

				D. L. Lange, J. R. Haywood, and C. Hinojosa-Laborde Role of the Adrenal Medullae in Male and Female DOCA-Salt Hypertensive Rats Hypertension, January 1, 1998; 31(1): 403 - 408. [Abstract] [Full Text] [PDF]

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