Physiology & Biophysics

Pamela K. Carmines, Ph.D

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ACADEMIC DEGREES:

Graduate School – Ph.D. 1982, Indiana University
Post-doctoral Training – 1982-1985, University of Alabama at Birmingham

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Contact Name:  Pamela K. Carmines
Phone Number: 402-559-9343
e-mail address: pcarmines@unmc.edu

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• GRANT SUPPORT (last 3 years):

Previous:

NIH (T32 HL07888) – Cardiovascular Research Training Program. Mentor. 07/01/98-06/30/03.  Total Direct Costs $395,328.

NIH (R21 DK063416) – Renal Cortical Oxidative and Nitrosative Stress in IDDM. Principal Investigator. 09/30/02-07/31/05. Total Direct Costs $587,000.

UNMC College of Medicine New Research Grant – Tyrosine Kinases in Renal Vasoconstrictor Signaling.  Principal Investigator. 02/15/05-02/14/06. Total Direct Costs $30,000.

Current:

NIH (R01 DK711552) -- Tyrosine Kinases in Renal Vasoconstrictor Signaling. Principal Investigator. 01/18/06-12/30/10.  Total Direct Costs $1,025,000.

NIH (R01 DK059869) – Impact of Puberty on the Kidney in Diabetes.  Co-Investigator. 08/01/01-07/31/06. Total Direct Costs $1,125,000.

NIH (R01 HL079587) – Cerebrovascular Disease in Type 1 Diabetes. Co-Investigator. 09/30/04-08/31/08.  Total Direct Costs $1,000,000.

NIH (R01 AA11288) – Cerebral Microcirculation during Alcohol Consumption.  Co-Investigator. 05/01/05-04/30/09. Total Direct Costs $875,000.

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• PUBLICATIONS (last 3-5 years):

Carmines PK, Fallet RW, Che Q, and Fujiwara K. Tyrosine kinase involvement in renal arteriolar constrictor responses to angiotensin II.  Hypertension 37: 569-573, 2001.
 

Fallet RW, Bast JP, Fujiwara K, Ishii N, Sansom SC, and Carmines PK. Influence of Ca²⁺-activated K⁺ channels on rat renal arteriolar responses to depolarizing agonists.  Am J Physiol Renal Physiol 280: F583-F591, 2001.

 

Patel KP and Carmines PK. Renal interstitial hydrostatic pressure and sodium excretion during acute volume expansion in diabetic rats.  Am J Physiol Regul Integr Comp Physiol 281: R239-R245, 2001.
 

Ishii N, Patel KP, Lane PH, Taylor T, Bian K, Murad F, Pollock JS, and Carmines PK. Nitric oxide synthesis and oxidative stress in the renal cortex of rats with diabetes mellitus.  J Am Soc Nephrol 12: 1630-1639, 2001.
 

Carmines PK and Fujiwara K. Altered electromechanical coupling in the renal microvasculature during the early stage of diabetes mellitus.  Clin Exp Pharmacol Physiol 29: 143-148, 2002.
 

Harrison-Bernard LM, Imig JD, and Carmines PK. Renal AT₁ receptor protein expression during the early stage of diabetes mellitus in the rat.  Int J Experimental Diab Res 3: 97-108, 2002.
 

Ishii N*, Fujiwara K*, Patel KP, Lane PH, and Carmines PK. Renal cortical nitric oxide synthase activity during maturational growth in the rat.  Pediatric Nephrol 17: 591-596, 2002. (*contributed equally to this work.)
 

Che Q and Carmines PK. Angiotensin II triggers EGFR tyrosine kinase-dependent Ca²⁺ influx in afferent arterioles.  Hypertension 40: 700-706, 2002.
 

Pluznick JL, Wei P, Carmines PK, and Sansom SC.  Renal fluid and electrolyte handling in BK_Ca-b1^–/– mice.  Am J Physiol Renal Physiol 284: F1274-F1279, 2003.
 

Ishii N, Ikenaga H, Carmines PK, Aoki Y, Ogawa Z, Saruta T, and Suga T. High glucose augments arginase activity and nitric oxide production in the renal cortex.  Metabolism 53: 868-874, 2004.
 

Lee DL, Sasser JM, Hobbs JL, Boriskie A, Pollock DM, Carmines PK, and Pollock JS. Posttranslational regulation of NO synthase activity in the renal medulla of diabetic rats.  Am J Physiol Renal Physiol 288: F82-F90, 2005.
 

Fallet RW, Ikenaga H, Bast JP and Carmines PK. Relative contributions of Ca²⁺ mobilization and influx in renal arteriolar contractile responses to arginine vasopressin.  Am J Physiol Renal Physiol 288: F545-F551, 2005.
 

Che Q and Carmines PK. Src family kinase involvement in rat preglomerular microvascular contractile and [Ca²⁺]_i responses to ANG II.  Am J Physiol Renal Physiol 288: F658-F664, 2005.
 

Pollock JS and Carmines PK. NOS3 regulation: Renal tubular epithelial cells are not simply large endothelial cells.  Hypertension 47: 19-21, 2006.
 

Ishii N, Ikenaga H, Carmines PK, Takada N, Okazaki T, Nagai T, Maeda T, Aoki Y, Saruta T, and Katagiri M. Impact of angiotensin-converting enzyme inhibition on renal cortical nitrotyrosine content during increased extracellular glucose concentration.  Clinical Biochemistry (In Press)
 

Carmines PK, Bast JP and Ishii N. Altered renal microvascular function in early diabetes.  In: Contemporary Diabetes — The Diabetic Kidney, edited by Cortes P and Mogensen CE. Totowa, NJ: Humana Press. 2006, p. 23-36.

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Predoctoral Trainees

1987-88	Peter J. Veldkamp, M.S. 1988 (Physician; location unknown)
1990-91	Joseph M. Ortenberg (Physician, Cardiovascular Diseases; Fort Worth, Texas)
1996-98	Joseph P. Bast (current UNMC medical student)
1997	Gwynn C. Schoonmaker (Internship, Medicine; University of Maryland, Baltimore)
2000-04	Qi Che, M.D. (Ph.D. expected in May 2004)

Postdoctoral Trainees

1987-90	Edward W. Inscho, Ph.D. (Professor, Physiology; Medical College of Georgia)
1990-93	Kazuhisa Ohishi, M.D., Ph.D. (Physician, Nephrology/Rheumatology; Hamamatsu Medical Center, Japan)
1990-93	Lisa M. Harrison-Bernard, Ph.D. (Associate Professor, Physiology; Louisiana St. University Health Science Center, New Orleans, LA)
1992-93	Tsuneo Takenaka, M.D., Ph.D. (Physician, Medicine/Nephrology; Saitama Med. School, Japan)
1993-94	Shari McArdle, Ph.D. (present location unknown)
1994-96	Hideki Ikenaga, M.D., Ph.D. (Private Practice Physician, Medicine/Nephrology; Otawara Redcross Hospital, Japan)
1996-98	Naohito Ishii, M.A., Ph.D. (Assistant Professor, Clinical Chemistry, Kitasato Univ. School of Allied Health Sciences, Japan)
1998-01	Keiji Fujiwara, M.D., Ph.D. (Physician, Medicine/Nephrology; Otawara Redcross Hospital, Japan)
2006-present	Qin Fang, M.D., Ph.D. (Postdoctoral Fellow, Department of Cellular & Integrative Physiology, UNMC)

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Research in this laboratory probes the integrative and cellular events that determine renal microvascular tone, focusing particular interest on the afferent and efferent glomerular arterioles. Within this context, we are working to delineate the mechanisms underlying renal arteriolar vasoconstrictor responses to the primary sodium- and water-retaining peptide hormones, angiotensin II and arginine vasopressin. For example, our recent studies have revealed that cSrc-mediated crosstalk between the G protein-coupled AT₁ receptor and the EGF receptor contributes to Ca²⁺ influx and contraction of preglomerular microvascular smooth muscle cells in response to angiotensin II. This observation implicates tyrosine kinases in the short-term control of renal vascular resistance. We are also addressing the postulate that insulin-dependent diabetes mellitus adversely influences renal function via pathophysiological alterations in the basic mechanisms controlling renal arteriolar function. Our accumulating observations indicate that afferent arteriolar smooth muscle tone is tightly linked to membrane potential, while efferent arteriolar tone regulated without dependence on membrane potential. Moreover, disruption of electromechanical coupling appears to contribute to the selective afferent arteriolar dysfunction that occurs during the early stage of diabetes. We have also provided evidence of deranged nitric oxide modulation of renal arteriolar tone and vasoconstrictor responsiveness during diabetes. The underlying mechanism involves oxidative stress resulting in an imbalance between nitric oxide production and degradation, and likely contributes to eventual development of diabetic nephropathy. Current studies are exploring the source and functional consequences of renal oxidative and nitrosative stress in diabetes, including the postulate that reactive oxygen species exert a direct effect on the intracellular signaling mechanisms controlling the contractile status of vascular smooth muscle and the Na⁺ transport function of the epithelial components of nephron.

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• SPECIALIZED LABORATORY/CLINICAL RESEARCH RESOURCES:

Microscope-based quantitative fluorescence microscopy system for monitoring of intracellular ion concentrations using ratiometric fluorescent probes.

Patch clamp techniques for studying ion channel function at the single cell level.
In vitro videomicroscopic analysis of renal arteriolar contractile responses.
Biochemical assays (enzyme activity, superoxide production, western blot, immunoprecipitation).

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