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.

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, immunocytochemistry, cell culture, kinase assays, animal surgery, blood pressure measurement and, of course, pharmacology!

Current Projects

1. Function of intracellular 5-HT
2. Alteration of 5-HT receptor subtype(s) in high pressure
3. Mechanism of blood pressure fall to 5-HT in chronic infusion
4. Endothelin signalling in arteries and veins: heterodimerization of ETA and ETB receptor
5. Development of venous specific protein expression in the mouse
6. Inflammatory profile of artery vs vein
7. Arterial versus venous function in hypertension

Selected Achievements since 2001:

Editorial Boards

• American Journal of Physiology: Heart, Lung and Circulatory
• American Journal of Physiology: Regulatory, Integrative and Comparative
• Clinical and Experimental Pharmacology and Physiology
• Clinical Science
• 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
• Bowditch Awardee of American Physiology Society, 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
• ASPET Centennial Celebration Planning Committee, 2004-2008
• Chair, Graduate Recruitment and Education Committee, 2005-2007
• 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 2003

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., 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.