Contact Info:Email: wattss@msu.edu Phone: (517) 353-3724 Fax: (517) 353-8915

Research Synopsis

The disease of hypertension affects approximately 20-30% of the world’s population, and hypertension continues to be a killer because of placing individuals at a higher risk for heart disease, stroke and kidney failure. Our laboratory is dedicated towards understanding the mechanisms by which arteries and veins contribute to this disease, in the hopes of developing novel treatments for hypertension. Arteries and veins contain smooth muscle, and thus have the ability to contract and change the size of their diameter. We have a history of investigating ‘non-classical’ pathways or signal transduction mechanisms for smooth muscle contraction. For example, 5-hydroxytryptamine or 5-HT has long been disputed as having the ability to alter blood vessel tone in vivo; we take the stance that it can. At the present, our laboratory has three on-going scientific projects, all of which revolve around understanding vessel dysfunction in hypertension:

1) Role of 5-HT (serotonin, 5-hydroxytryptamine) and the 5-HT transporter in control of normal arterial tone and blood pressure; upregulation and altered function of 5-HT receptors in hypertension; determination of whether a local 5-HT generating system exists in peripheral smooth muscle.

2) Endothelin (ET-1) in control of venomotor tone in hypertension. Go to www.ppg.msu.edu for more information.

3) Role of the enzyme phosphoinositide –3-Kinase in development of increased total peripheral resistance in hypertension.

We use a multi-faceted technical and integrated approach towards studying these diseases so as to understand the mechanism from a molecular to a whole animal level. Techniques in our lab include: isolated tissue bath system to measure smooth muscle contraction, myograph to measure small artery contraction, Western analyses, real time RT-PCR, HPLC, immunohistochemistry, kinase assays, animal surgery and blood pressure measurement.

Current Projects

1. Function of arterial 5-HTT transporter
2. Alteration of 5-HT receptor subtype(s) in high pressure
3. Vascular function in the mouse
4. Endothelin signalling in arteries and veins
5. Development of venous specific protein expression in the mouse
6. Arterial versus venous function in hypertension

Selected Achievements since 2001:

Editorial Boards
American Journal of Physiology: Heart, Lung and Circulatory
Biochemical Pharmacology
Clinical and Experimental Pharmacology and Physiology
Current Reviews of Hypertension
Hypertension
Journal of Pharmacology and Experimental Therapeutics, Associate Editor

Honors/Awards
PhRMA Faculty Development Award, 1998-2000
Young Scholar Award, American Society of Hypertension
Nominated for ASPET Councilor, 2001
Established Investigator of the American Heart Association, 2002
Howard Hughes Medical Investigator Nominee, Michigan State University, 2004
HM Study Section Member, 2004-2008

ASPET
Member, Recruitment and Education Committee, 1999-2005
Member, Subcommittee on Graduate Student Convocation, 1999-2002
Symposium Organizer, “Functions of Phosphoinositide-3-kinase in the Cardiovascular System,” EB ’02 Meeting, New Orleans, LA
Organizer, ASPET Graduate Student Convocation, EB ’02 Meeting, New Orleans, LA
Organizer, ASPET 2004 Graduate Symposium, “Preserving and Promoting Your Discipline,” EB ’04 Meeting, Washington, DC
Elected to ASPET Centennial Celebration Planning Committee, 2004-2007
Chair, Graduate Recruitment and Education Committee, 2005-2008

Council for High Blood Pressure, and American Heart Association (AHA)
Member, AHA Student Summer Fellow Task Force, 2000-present
Chair, Sessions on “Vasoactive Mechanisms,” 55th Annual Fall Conference and Scientific Sessions, 2001
Member, AHA Fall Program Committee, 2001-2004
Chair, Session on “Receptors and Signal Transduction,” 56th Annual Fall Conference and Scientific Sessions, 2002
Member, AHA Midwest Affiliate Research Committee, 2002-2003
Member, Publications Committee, 2002-2003
Co-Chair, “Punch/Counterpunch: How to critically evaluate a manuscript and successfully respond to a critical evaluation,” 56th Annual Fall Conference and Scientific Sessions (in association with the Council on the Kidney in Cardiovascular Disease), 2002
Member, AHA Greater Midwest Affiliate Research Committee, 2003-2006
Chair, Session on “Vascular Remodeling and Dysfunction,” 57th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research in association with the Council on the Kidney in Cardiovascular Disease, 2003
Organizer and Moderator: “Spinning Your Web: Networking, Networking, Networking,” 57th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research in association with the Council on the Kidney in Cardiovascular Disease, 2003
Organizer, “The Anti-Trump: You’re Hired! Lessons on Landing Your First Academic Position” 58th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research in association with the Council on the Kidney in Cardiovascular Disease, 2004
Chairperson, “Cardiovascular Remodeling and Dysfunction,” 58th Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research in association with the Council on the Kidney in Cardiovascular Disease, 2004
Organizer of 1st Trainee Mixer, Annual Fall Conference and Scientific Sessions of the Council for High Blood Pressure Research in association with the Council on the Kidney in Cardiovascular Disease, 2004
Vice-Chair, Hypertension Summer School, Maritime Academy in Maine, 2004-05
Chair, Hypertension 2007 Summer School (Ft. Collins, CO)
Chair, Trainee Advocacy committee, CHBPR

Other
Member, Pharmaceutical Research and Manufacturers Association Foundation (PhRMA) Basic Pharmacology Research Advisory Board, 2001-present
PhRMA Foundation “Health for Life” Campaign, Fall/Winter Newsweek Ad, 2001
International Union of Pharmacology 5-HT Receptor Nomenclature Committee, 2002-present
Member, American Physiological Society Awards Committee, 2002-present
Chair, Session on “Vasoactive Mechanisms,” XVth Meeting of the International Association of Hypertension, April, 2003
US Councilor, International Serotonin Club, 2003-2005
Charter Member of Hypertension and Microbiology Study Section, NIH, NHLBI October 2004, 2004-2008
Elected, American Physiological Society, CV Section Nominating Committee, 2004-2007
Elected, USA 5-HT Councilor, 2004-2006
Chairperson, “Cell Biology/Growth Factors,” 15th Meeting of the American Society of Hypertension, New York, NY, 2004

Selected Samples of Publications Since 2001

Ballew JR, Watts SW, Fink GD: Effects of salt intake and angiotensin II on vascular reactivity to endothelin-1. J. Pharmacol. Exp. Ther. 296(2): 345-350, 2001.

McKune C, Watts SW: Characterization of the serotonin receptor mediating contraction in the mouse thoracic aorta and signal pathway coupling. J. Pharmacol. Exp. Ther. 297(1): 88-95, 2001.

Xu H, Fink GD, Chen A, Watts SW, Galligan JJ: Nitric oxide-independent effects of tempol on sympathetic nerve activity and blood pressure in normotensive rats. Amer. J. Physiol. 281(2): H975-H980, 2001.

Atkins, K.B., Johns, D., Watts, S., Clinton Webb, R. and Brosius III, F.C.: Decreased vascular glucose transporter expression and glucose uptake in DOCA-salt hypertension. J. Hypertens. 19(9): 1581-1587, 2001.

Florian, J.A., Dorrance, A., Webb, R.C. and Watt, S.W.: Mineralocorticoids upregulate arterial contraction to epidermal growth factor. Amer. J. Physiol. 281(3): R878-R886, 2001.

Watts, S.W., Yang, P., Banes, A.K. and Baez, M.: Activation of Erk mitogen-activated protein kinase proteins by vascular serotonin receptors. J. Cardiovasc. Pharmacol. 38(4): 539-551, 2001.

Banes, A.K. and Watts, S.W.: Enhanced contraction to 5-hydroxytryptamine is not due to “unmasking” of 5-hydroxytryptamine1B receptors in the mesenteric artery of the deoxycorticosterone-salt rat. Hypertension 38: 891-895, 2001.

Banes, A.K.L., Loberg, R.D., Brosius, F.C. and Watts, S.W.: Inability of serotonin to activate the c-Jun-N-terminal kinase and p38 kinase pathways in rat aortic vascular smooth muscle cells. BMC Pharmacology 1: 8, 2001.

Northcott, C., Florian, J.A., Dorrance, A. and Watts, S.W.: Arterial epidermal growth factor receptor expression in DOCA-salt hypertension. Hypertension 38: 1337-1341, 2001.

Johnson RJ, Fink GD, Watts SW, Galligan JJ: Endothelin receptor function in mesenteric veins from deoxycorticosterone acetate-salt hypertension. Hypertension 39(3): 825-829, 2002.

Watts SW: Serotonin-induced contraction in mesenteric resistance arteries: Signaling and changes in deoxycorticosterone acetate-salt hypertension. Hypertension 39(3): 825-829, 2002.

Johnson RJ, Fink GD, Watts SW, Galligan JJ: Endothelin receptor function in mesenteric veins from deoxycorticosterone acetate-salt hypertensive rats. J. Hypertension 20(4): 665-676, 2002.

Banes AB, Watts SW: Upregulation of arterial serotonin1B and 2B receptors in DOCA-salt hypertension. Hypertension 39: 394-398, 2002.

Watts SW, Fink GD, Northcott CA, Galligan JJ: Endothelin-1-induced venous contraction is maintained in DOCA-salt hypertension; studies with receptor agonists. Brit. J. Pharmacol. 137(1): 69-79, 2002.

Northcott CA, Poy MN, Najjar SM, Watts SW: Phosphoinositide-3-kinase mediates enhanced spontaneous and agonist-induced contraction in aorta of deoxycortisone acetate-salt hypertensive rats. Circ. Res. 91(4): 360-369, 2002.

Russell A, Banes A, Berlin H, Fink GD, Watts SW: 5-Hydroxytryptamine2B receptor function is enhanced in the N?-L-arginine hypertensive rat. J. Pharmacol. Exp. Ther. 303(1): 179-187, 2002.

Li L, Fink GD, Watts SW, Northcott CA, Galligan JJ, Pagano PJ, Chen AF: Endothelin-1 increases vascular superoxide via ETA-NADPH oxidase pathway in low-renin hypertension. Circulation 107(7): 1053-1058, 2003.

Loberg R, Northcott C, Watts SW, Brosius F: PI-3-Kinase-induced hyperreactivity in DOCA-salt hypertension is independent of GSK-3 activity. Hypertension 41(4): 898-902, 2003.

Li L, Watts SW, Banes AK, Galligan JJ, Fink GD, Chen AF: NADPH oxidase-derived superoxide augments endothelin-1 induced venoconstriction in mineralocorticoid hypertension. Hypertension 42(3): 316-321, 2003.

Banes AKL, Watts SW: Arterial expression of 5-HT2B and 5-HT1B receptors during development of DOCA-salt hypertension. BMC Pharmacology 3(1): 12-37, 2003.

Northcott CA, Watts SW, Hsueh W: Vasoactive growth factors and adhesion molecules. In “Hypertension Primer,” 3rd edition (J.L. Izzo and H.R. Black, eds.), p. 66-69, 2003.

Northcott CA, Watts SW: Low [Mg2+]e enhances arterial spontaneous tone via phosphatidylinositol 3-kinase in DOCA-salt hypertension. Hypertension 43(1): 125-129, 2004.

Northcott CA, Hayflick JS, Watts SW: PI3-Kinase upregulation and involvement in spontaneous tone in arteries from DOCA-salt rats: Is p110? the culprit? Hypertension 43(4): 885-890, 2004.

Northcott CA, Watts SW: Does hypomagnesemia have an adaptive role in hypertension? [Response to Letter to the Editor]. Hypertension 43(4): E29, 2004.

Watts SW, Thompson JM: Characterization of contractile 5-hydroxytryptamine receptor in the renal artery of the normotensive rat. J. Pharmacol. Exp. Ther. 309(1): 165-172, 2004.

Thakali K, Fink GD, Watts SW: Arteries and veins desensitize differently to endothelin-1. J. Cardiovasc. Pharmacol. 43: 387-393, 2004.

Slovut DP, Mehta S, Dorrance AM, Brosius FC, Watts SW, Webb RC: Increased vascular sensitivity and connexin43 expression after sympathetic denervation. Cardiovasc. Res. 62(2): 388-396, 2004.

Ni W, Li M, Thakali K, Fink GD, Watts SW: The fenfluramine metabolite (+)-norfenfluramine is vasoactive. J. Pharmacol. Exp. Ther. 309(2): 845-852, 2004.

Dai X, Galligan JJ, Watts SW, Fink GD, Kreulen DL: Increased O2- production and upregulation of ETB receptors by sympathetic neurons in DOCA-salt hypertensive rats. Hypertension 43(5): 1048-1054, 2004.

Ni W, Thompson JM, Northcott CA, Lookingland KJ, Watts SW: The serotonin transporter is present and functional in peripheral arterial smooth muscle. J. Cardiovasc. Pharmacol. 43(6): 770-781, 2004.

Watts SW: C3 or not C3. That is the question. Hypertension 44(1): 25-26, 2004.

Wehrwein EA, Northcott CA, Loberg RD, Watts SW: Rho/Rho-kinase and phosphoinositide 3-kinase are parallel pathways in the development of spontaneous arterial tone in deoxycorticosterone acetate-salt hypertension. J. Pharmacol. Exp. Ther. 309(3): 1011-1019, 2004.

Atkins, K. B., Northcott, C. A., Watts, S. W. and Brosius, F. C.: Effect of PPARg ligands on vascular smooth muscle marker expression in hypertensive and normal arteries, Am J Physiol. Heart Circ, 288:H235-H243, 2005.

Wang H, Chen AF, Watts SW, Galligan JJ, Fink GD: Endothelin in the splanchnic vascular bed of DOCA-salt hypertensive rats. Amer. J. Physiol., in press, 2004.

Watts SW, Kanagy NL, Lombard J: Receptor-mediated events in the microcirculation. In “Microcirculation: Handbook of Physiology,” Oxford University Press, in press, 2004.

Wang, H., Galligan, J. J., Chen, A. L., Watts, S. W. and Fink, G. D.: Endothelin in the splanchnic vascular bed of DOCA-salt hypertensive rats, Am. J. Physiol Heart Circ, 288:H72-H736, 2005.

Toews, M.L., Watts, S. W. and Beckman, B. S.: Preserving and promoting our discipline: pharmacology students speak out. Mol. Interven. 5:4-7, 2005.

Watts, S. W.: 5-HT in Systemic Hypertension: friend, foe or fantasy? Clinical Sci., 108:399-412, 2005.

Thakali, K., Demel, S. L., Fink, G. D. and Watts, S. W.: Endothelin-1 (ET-1)-induced contraction in veins is independent of hydrogen peroxide (H2O2), Am. J. Physiology Heart Circ, 289:H1115-1122, 2005.

Ni, W., Wilhelm, C. S., Bader, M., Murphy, D. L., Lookingland, K. and Stephanie W. Watts: (+)-Norfenfluramine-induced arterial contraction is not dependent on endogenous 5-HT or 5-HTT, J. Pharmacol. Exp. Ther., 314L953-960, 2005.

Northcott, C. A. and Watts, S. W.: Upregulated function of phosphoinositide-3-kinase (PI-3-K) in genetically hypertensive rats: a moderator of arterial hypercontractility, in press, Clin. Exper. Physiol. Pharmacol., 2005.

Xu, H., Bian, X., Watts, S. W., Hlavacova, A. and Galligan, J. J.: Activation of vascular BK channel by tempol in DOCA-salt hypertensive rats, in press, Hypertension, 2005.

Watts, S. W.: Vasoconstriction caused by the ATP syntahse subunit coupling factor 6: a new function for an historical enzyme, in press, Hypertension, 2005.

Perez-Rivera, A., Watts, S. W., Fink, G. D.and Galligan, J. J.: Alpha1 adrenergic receptor function and protein expression in arteries and veins from normal and hypertensive mice, in revision, J. Pharmacol. Exp. Ther., 2005.

Huang, J, Lin, S. C., Watts, S. W. and Sarkar, R.: Antiproliferative effects of nitric oxide and peroxynitrite in vascular smooth muscle cells: role of redox signaling and poly(adp-ribose) polymerase (PARP) activation, submitted, Hypertension, 2005.

Pervaiz, M. H., Watson, E. R., Rondelli, C., Thakali, K., Fink, G. D. and Watts, S. W.: Arterial but not venous remodling in hypertension: evidence from studies of matrix metalloproteinase 2, submitted, Hypertension, 2005.

Ni, W. and Watts, S. W.: 5-HT in the cardiovascular system: focus on the serotonin transporter (SERT), submitted, Clin. Exp. Pharmacol. Physiol, 2005.

Northcott, C. A. and Watts, S. W.: Upregulated function of phosphoinositide-3-kinase (PI-3-K) in genetically hypertensive rats: a moderator of arterial hypercontractility, Clin. Exper. Physiol. Pharmacol., 32:851-858, 2005.

Xu, H., Bian, X., Watts, S. W., and Hlavacova, A.: Activation of vascular BK channel by tempol in DOCA-salt hypertensive rats, Hypertension, 46:1154-1162, 2005.

Watts, S. W.: Vasoconstriction caused by the ATP synthasee subunit coupling factor 6: a new function for an historical enzyme, Hypertension, 46:1100-1102, 2005.

Thakali, K., Davenport, L., Fink, G. D. and Watts, S. W.: Pleiotropic effects of hydrogen peroxide in arteries and veins from normotensive and deoxycorticosterone acetate-salt hypertensive rats, Hypertension, 47:482-487, 2006.

Ni, W. and Watts, S. W.: 5-HT in the cardiovascular system: focus on the serotonin transporter (SERT), Clin. Exp. Pharmacol. Physiol, 33:575-583, 2006.

Thakali K. M., Lau, Y., Fink, G. D., Galligan, J. J., Chen, A. F. and Watts, S. W.: Mechanisms of hypertension induced by nitric oxide (NO) deficiency: focus on venous function, J. Cardiovasc Pharmacol., 47:742-740, 2006.

Ni, W., Lookingland, K. and Watts, S. W.: Arterial 5-HT transporter function is impaired in DOCA-salt hypertensive but not spontaneously hypertensive rats, Hypertension, 48:134-140, 2006.

Ogden, K., Thompson, J. M., Hickner, Z., Huang, T., Tang D. D. and Watts, S. W.: A new signaling paradigm for serotonin: Use of Crk-Associated substrate in arterial contraction, in press, Am. J. Physiology Heart Circ Phys, 2006.

Ni, W.,Lookingland, L. and Watts, S. W.: Response to “Blood pressure in mutant rats lacking the 5-hydroxytryptamine (5-HT) transporter, Hypertension, in press, 2006.

Watts, S. W., Kanagy, N. L. and Lombard, J.: Receptor-mediated Events in the Microcirculation, in Microcirculation: Handbook of Physiology, Oxford University Press, 2005.

Thakali, K., Galligan, J. J., Fink, G. D. and Watts, S. W.: Arterial and Venous function in hypertension: a vascular focus, Comprehensive Hypertension, Elsevier, 2006 or 2007.

Szasz, T., Thakali, K., Fink, G. D. and Watts, S. W.: A comparison of arteries and veins in oxidative stress: producers, destroyers, function and disease, in press, Soc. Exp. Biol. Med, 2006.

Thakali, K., Davenport, L., Fink, G. D. and Watts, S. W.: Common signaling pathways mediated hydrogen peroxide induced contraction of rat thoracic aorta and vena cava, J. Pharmacol. Exp. Ther., in press, 2006.