Health  Vol.2 No.8 , August 2010
Sex differences in cardiovascular control by nitric oxide in normotensive and hypertensive rats
Abstract: R Nitric oxide probably plays an important role in mechanisms determining sexual dimorphism in the development of cardiovascular diseases, including hypertension. Because stress together with gender are significant cardiovascular risk factors, we studied the role nitric oxide in car-diovascular regulation in male and female nor-motensive and hypertensive rats under normal and stress conditions. Experiments were per-formed in mongrel normotensive and hyperten-sive (two kidney, one clip) rats of both sexes, weighing 200-250g. The study of mean arterial pressure and heart rate was carried out: 1) under control condition; 2) during nitric oxide blo- ckade by NG-nitro-L-arginine-methyl ester (L-NAME, 10 mg/kg, iv) 3) during 60 min immobilization stress and recovery; 4) during 60 min immobi-lization stress + L-NAME and recovery. We found that the severity of hypertension in fe-males was lower than in males. We also ob-served that both normotensive and hyperten-sive females demonstrated more favorable pat-tern of cardiovascular responses to stress. At rest, nitric oxide blockade increased the mean arterial pressure and decreased the heart rate more effectively in female normotensive and hypertensive rats than in male groups. During stress, nitric oxide blockade modified the stress- induced cardiovascular responses more sig-nificantly in female normotensive and hyper-tensive rats compared with male groups. Our data show that both normotensive and hyper-tensive females demonstrated the more effec-tive nitric oxide control of cardiovascular activ-ity under normal and especially stress condi-tions than male groups. This male-female dif-ference may be important mechanism respon-sible for greater in females vs. males of cardio-vascular resistance to stress and development of hypertension.
Cite this paper: nullSemyachkina-Glushkovskaya, O. , Anishchenko, T. , Kapralov, S. , Novikov, R. , Skvorcov, K. , Kuznecova, Y. and Kuznecova, A. (2010) Sex differences in cardiovascular control by nitric oxide in normotensive and hypertensive rats. Health, 2, 897-905. doi: 10.4236/health.2010.28133.

[1]   Beghetti, M., Sparling, C., Cox, P., Stephens, D. and Adatia, I. (2003) Inhaled NO inhibits platelet aggregation and elevates plasma but not intraplatelet cGMP in healthy human volunteers. American Journal Physiology -Heart and Circulatory Physiology, 285(2), H637-642.

[2]   Urao, N., Okigaki, M., Yamada, H., Aadachi, Y. Matsuno, K. and Matsui, A. (2006) Erythropoietin-Mobilized Endothelial Progenitors Enhance Reendothelialization via Akt-Endothelial Nitric Oxide Synthase Activation and Prevent Neointimal Hyperplasia. Circulation Research, 98(11), 1405-1411.

[3]   Sener, A. and Smith, F. (2001) Nitric oxide modulates arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner. American Journal Physiology-Heart and Circulatory Physiology, 280(5), H2255-H2263.

[4]   Herring, N., Danson, E. and Paterson, D. (2002) Cho-linergic control of heart rate by nitric oxide is site spe-cific. News Physiological Sciences, 17(6), 202-206.

[5]   Patel, K., Li, Y.-F. and Hirooka, Y. (2001) Role of nitric oxide in central sympathetic outflow. Experimental Bi-ology and Medicine, 226(9), 814-824.

[6]   Markov, K. (2001) Nitrogen oxide and the cardiovascular system. Uspechi Fiziologicheskikh Nauk, 32(3), 49-65.

[7]   Toda, N. and Okamura, T. (2003) The pharmacology of nitric oxide in the peripheral nervous system of blood vessels. Pharmacological Reviews, 55(2), 271-324.

[8]   Ignarro, L., Napoli, C. and Loscalzo, J. (2002) Nitric oxide donors and cardiovascular agents modulating the bioactivity of nitric oxide. Circulation Research, 90(1), 21-28.

[9]   Forte, P., Kneale, B., Milne, E., Chowienczyk, P., Johns-ton, A., Benjamin, N. and Ritter, J. (1998) Evidence for a difference in nitric oxide biosynthesis between healthy women and men. Hypertension, 32(4), 730-734.

[10]   Sader, M. and Celermajer, D. (2002) Endothelial function, vascular reactivity and gender differences in the cardio-vascular system. Cardiovascular Research, 53(3), 597- 604.

[11]   Kauser, K. and Rubanyi, G. (1994) Gender difference in bioassayable endothelium-derived nitric oxide from iso-lated rat aortae. American Journal of Physiology-Heart and Circulatory Physiology, 267(5), H2311-2317.

[12]   Skarsgard, P., van Breemen, C. and Laher, I. (1997) Es-trogen regulates myogenic tone in pressurized cerebral arteries by enhanced basal release of nitric oxide. American Journal of Physiology-Heart and Circulatory Physiology, 273(5), H2248-2256.

[13]   Knot, H., Lounsbury, K., Brayden, J. and Nelson, M. (1999) Gender differences in coronary artery diameter reflect changes in both endothelial Ca2+ and ecNOS ac-tivity. American Journal of Physiology-Heart and Cir-culatory Physiology, 276(3), H961- 969.

[14]   Laughlin, M., Welshons, W., Sturek, M., Rush, J., Turk, J., Taylor, J., et al. (2003) Gender, exercise training, and eNOS expression in porcine skeletal muscle arteries. Journal of Applied Physiology, 95(1), 250-264.

[15]   Glushkovskaya-Semyachkina, O., Anishchenko, T., Sind-yakova, T., Leksina, O. and Berdnikova, V. (2006) Sex- related differences in nitric oxide content in healthy and hypertensive rats at rest and stress conditions. Bulletin of Experimental Biology and Medicine, 142(1), 9-13.

[16]   Anishchenko, T., Glushkovskaya-Semyachkina, O., Ber- dnikova, V. and Sindyakova, T. (2007) Sex-related differences in cardiovascular stress-reactivity in healthy and hypertensive rats. Bulletin of Experimental Biology and Medicine, 143(2), 136-139.

[17]   Bondarenko, O., Bondarenko, N., Malyshev, I. and Manukhina, E. (2001) Antistress effect of nitric oxide. Biological Bulletin, 28(3), 387-393.

[18]   Dias, A. and Colombari, E. (2006) Central nitric oxide modulates hindquarter vasodilation elicited by AMPA receptor stimulation in the NTS of conscious rats. American Journal of Physiology-Regulatory Integrative Comparative Physiology, 290(5), R1330-R1336.

[19]   Anishchenko, T. and Igosheva. (1992) Sex differences in reactivity of conscious and anesthetized rats to surgical stress. Bulletin of Experimental Biology and Medicine, 113(1), 26-28.

[20]   Reckelhoff, J.F. (2001) Gender Differences in the Regula-tion of Blood Pressure. Hypertension, 37(4), 1199- 1223.

[21]   Coatmellec-Taglioni, G., Dausse, J., Ribière, C. and Giu- dicelli, Y. (2003) Sexual Dimorphism in cafeteria diet- induced hypertension is associated with gender-related difference in renal leptin receptor down-regulation. Journal of Pharmacology and Experimental Therapeu-tics, 305(1), 362-367.

[22]   Matthews, K., Katholi, C., McCreath, H., Whooley, M., Williams, D., Zhu, S. and Markovitz, J. (2004) Blood pressure reactivity to psychological stress predicts hy-pertension in the CARDIA study. Circulation, 110(1), 74- 78.

[23]   Anishchenko, T., Brill, G., Romanova, T. and Shorina, L.. (1995) Sex-related differences in the degree of lipid per-oxidation activation and resistance to cardiovascular damage induced by stress in rats. Bulletin of Experimen-tal Biology and Medicine, 119(4), 354-357.

[24]   Anishchenko, T., Brill, G., Romanova, T. and Igosheva, N. (1992) Sex differences in adrenocortical sensitivity and resistance to cerebral lesions in rats exposed to se-vere stress. Bulletin of Experimental Biology and Medi-cine, 114(10), 353-355.

[25]   Forte, P., Kneale, B., Milne, E., Chowienczyk, P., Johns-ton, A., Benjamin, N. and Ritter, J. (1998) Evidence for a difference in nitric oxide biosynthesis between healthy women and men. Hypertension, 32(4), 730-734.

[26]   Luiking, Y., Hallemeesch, M., Vissers, Y., Lamers, W. and Deutz, N. (2004) In vivo whole body and organ ar-ginine metabolism during endotoxemia (sepsis) is de-pendent on mouse strain and gender. The Journal of Nu-trition, 134(10), 2768S-2774S.

[27]   Forte, P., Copland, M., Smith, L., Milne, E., Sutherland, J. and Benjamin, N. (1997) Basal nitric oxide synthesis in essential hypertension. Lancet, 349(3), 837-842.

[28]   Tokuyama, H., Hayashi, K., Matsuda, H., Kubota, E., Honda, M. and Ozawa, Y. (2002) Stenosis-dependent role of nitric oxide and prostaglandins in chronic renal ische-mia. American Journal of Physiology-Renal Physiology, 282(1), F859-F865.

[29]   Rosyn, M., Speziale, E., Celentano, M., Vega, G., Da- miano, P. and Puyy, A. (2001) Serotonin hypersensitivity in aorta of two-kidney one clip hypertensive rats: Cal-cium contribution and prostanoids-nitric oxide interac-tions. Archives of Physiology and Biochemistry, 109(1), 32-37.

[30]   Puyo, A., Vega, G., Iraldi, A., Albornoz, L., Roson, M. and Scaglia, P. (1998) Atrial natriuretic factor in two kidney-two clip renovascular hypertension in the rat. Medicine (Buenos Aires), 58(2), 165-170.

[31]   Fozard, J. and Part, M. (1991) Hemodynamic responses to NG-monomethyl-L-arginine in spontaneously hyper-tensive and normotensive Wistar-Kyoto rats. British Journal Pharmacology, 102(4), 823-826.

[32]   McIntyre, M., Hamilton, C., Rees, D., Reid, J. and Dominiczak, A. (1997) Sex differences in the abundance of endothelial nitric oxide in a model of genetic hyper-tension. Hypertension, 30(6), 1517-1524.

[33]   Lacolley, P., Lewis, S. and Brody, M. (1991) L-NG- nitroar-ginine produces and exaggerated hypertension in anesthetized SHR. European Journal Pharmacology, 197(2-3), 239- 240.

[34]   Campese, V. (2000) The kidney and hypertension: Over 70 years of research. Journal of Nephrology, 19(6), 691- 698.

[35]   Orshal, J. and Khalil, R. (2004) Gender, sex hormones, and vascular tone. American Journal of Physiology- Regulatory Integrative Comparative Physiology, 286(2), R233-R249.

[36]   Ba, Z., Yokoyama, Y., Toth, B., Rue, L., Bland, K. and Chaudry, I. (2004) Gender differences in small intestinal endothelial function: Inhibitory role of androgens. Am- erican Journal of Physiology—Gastrointestinal Liver Physiology, 286(2), G452-G457.

[37]   Anishchenko, T. and Glushkovskaya-Semaychkina, O. (2003) Normalized entropy applied to the analysis of gender-related differences in parasympathetic cardiovas-cular control in normal and stressed rat. Physician and Technology, 32(1), 29-39.

[38]   Airaksinen, K., Ikaheimo, M., Linnaluoto, M., Tahvana-inen, K. and Huikuri, H. (1998) Gender difference in autonomic and hemodynamic reactions to abrupt coro-nary occlusion. Journal of American College of Cardiol-ogy, 31(2), 301-306.

[39]   De Ferrari, G., Vanoli, E., Stramba-Badiale, M., Hull, S. and Foreman, R. (1991) Vagal reflexes and survival during acute myocardial ischemia in conscious dogs with healed myocardial infarction. American Journal Physiology—Heart and Circulatory Physiology, 261(1), H63- H69.