Abstract
Aim:
To study the effect of genistein (GST) on carotid baroreceptor activity (CBA).
Methods:
The functional curve of carotid baroreceptor (FCCB) was constructed and the functional parameters of carotid baroreceptor were measured by recording sinus nerve afferent discharge in anesthetized male rats with perfused isolated carotid sinus.
Results:
GST at 50, 100, and 200 μmol/L inhibited the CBA, which shifted FCCB to the right and downward, with a marked decrease in peak slope and peak integral value of carotid sinus nerve discharge in a concentration-dependent manner. Pretreatment with 100 μmol/L NG -nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not affect the effect of GST on CBA. Pretreatment with 500 nmol/L Bay K8644, an agonist of calcium channels, could completely abolish the effect of GST on CBA. A potent inhibitor of tyrosine phosphatase, sodium orthovanadate (1 mmol/L), could attenuate the inhibitory effect of GST.
Conclusion:
GST inhibits CBA, and the effect may be mediated by protein tyrosine kinase inhibition and a decrease in Ca2+ influx through the stretch-activated channels.
Similar content being viewed by others
Article PDF
References
Anthony MS, Clarkson TB, Williams JK . Effects of soy isoflavones on atherosclerosis: potential mechanisms. Am J Clin Nutr 1998; 68 ( Suppl): S1390–3.
Anthony MS, Clarkson TB . Association between plasma isoflavone and plasma lipoprotein concentrations. J Med Food 1999; 2: 263–6.
Figtree GA, Griffiths H, Lu YQ, Webb CM, Macleod K, Collins P . Plant-derived estrogens relax coronary arteries in vitro by a calcium antagonistic mechanism. J Am Coll Cardiol 2000; 35: 1977–85.
Akiyame T, Ishida J, Nakagawa S, Ogawara H, Watanabe S, Itoh N, et al. Genistein: a specific inhibitor of tyrosine-specific protein kinases. J Biol Chem 1987; 262: 5592–5.
Fotsis T, Pepper M, Adlercreuta H, Fleischmann G, Hase T, Montesano R, et al. Genistein, a dietary-derived inhibitor of in vitro angiogenesis. Proc Natl Acad Sci USA 1993; 90: 2690–4.
Honore EK, Williams JK, Anthony MS, Clarkson TB . Soy isoflavones enhance coronary vascular reactivity in atherosclerotic female macaques. Fertil Steril 1997; 67: 148–54.
Li HF, Wang LD, Qu SY . Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo. Acta Pharmacol Sin 2004; 25: 313–8.
Ji ES, Zhang LH, Wang YH, Yue H, He RR . Responses of regional vascular beds to local injection of genistein in rats. Acta Physiol Sin 2003; 55: 255–9.
Ji ES, Yue H, Wu YM, He RR . Effects of phytoestrogen genistein on myocardial ischemia/reperfusion injury and apoptosis in rabbits. Acta Pharmacol Sin 2004; 25: 306–12.
Ji ES, Wang C, He RR . Effects of genistein on intracellular free calcium concentration in guinea pig ventricular myocytes. Acta Physiol Sin 2004; 56: 204–9.
Zhao G, Ho SY . The facilitating effect of atrial natriuretic peptide in the carotid sinus baroreflex function. Acta Physiol Sin 1991; 43: 360–7.
Zhang H, Liu YX, Wu YM, Wang ZM, He RR . Capsaicin facilitates carotid sinus baroreceptor activity in anesthetized rats. Acta Pharmacol Sin 2004; 25: 1439–43.
Yi XL, Fan ZZ, He RR . An automatic system controlled by computer for carotid sinus perfusion. Chin J Appl Physiol 1993; 9: 156–9.
Hohler B, Mayer B, Kummer W . Nitric oxide synthase in the rat carotid body and carotid sinus. Cell Tissue Res 1994; 276: 559–64.
Li Z, Chapleau MW, Bates JN, Bielefeldt K, Lee HC, Abboud FM . Nitric oxide as an autocrine regulator of sodium currents in baroreceptor neurons. Neuron 1998; 20: 1039–49.
Chapleau MW, Hajduczok G, Sharma RV, Wachtel RE, Cunningham JT, Sullivan MJ, et al. Mechanisms of baroreceptor activation. Clin Exp Hypertens 1995; 17: 1–13.
Wang S, Fan ZZ, He RR . 17β-Estradiol inhibits carotid sinus baroreceptor activity in anesthetized male rats. Acta Pharmacol Sin 2001; 22: 440–4.
Grigg P . Biophysical studies of mechanoreceptors. J Appl Physiol 1986; 60: 1107–15.
Drummond HA, Welsh MJ, Abboud FM . EnaC subunits are molecular components of the arterial baroreceptor complex. Ann NY Acad Sci 2001; 940: 42–7.
Qin XM, Fan ZZ, He RR . Agmatine inhibits the afferent activity of carotid baroreceptor in rats. Acta Physiol Sin 2001; 53: 137–41.
Liu YX, Zhang H, Dong JH, Li Q, He RR . Cholecystopinin octapeptide inhibits carotid sinus baroreceptor activity in rats. Chin J Pharmacol Toxicol 2005; 19: 18–23.
Qin XM, He RR . Role of calcium in the mechanism underlying the inhibitory effect of streptomycin on carotid sinus baroreflex in rats. Acta Physiol Sin 2000; 52: 463–7.
Hughes A, Wijetunge S . Role of tyrosine phosphorylation in excitation-contraction coupling in vascular smooth muscle. Acta Physiol Scand 1998; 164: 457–69.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project supported by a grant from Natural Science Foundation of Hebei Province of China (No 303467) and National Natural Science Foundation of China (No 304005).
Rights and permissions
About this article
Cite this article
Ma, Hj., Liu, Yx., Wang, Fw. et al. Genistein inhibits carotid sinus baroreceptor activity in anesthetized male rats. Acta Pharmacol Sin 26, 840–844 (2005). https://doi.org/10.1111/j.1745-7254.2005.00127.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2005.00127.x