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1. Evaluating Knowledge to Support Climate Action: A Framework for Sustained Assessment Evaluating Knowledge to Support Climate Action: A Framework for Sustained Assessment

Author

Moss, RH, Avery, S, Baja, K, Burkett, M, William, S, Chischilly, AM, Dell, J, Fleming, PA, Geil, K, Jacobs, K, Jones, A, Knowlton, K, Koh, J, Lemos, MC, Melillo, J, Pandya, R, Richmond, TC, Scarlett, L, Snyder, J, Stults, M, Waple, A, Whitehead, J, Zarrilli, D, Ayyub, B, Fox, J, Ganguly, A, Joppa, L, Julius, S, Kirshen, P, Kreutter, R, McGovern, A, Meyer, R, Neumann, J, Solecki, W, Smith, J, Tissot, P, Yohe, G, and Zimmerman, R

Subjects
Climate Action, North America, Climate prediction, Planning, Policy, Risk assessment, Societal impacts
Abstract

As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal ‘‘climate assessment consortium’’ to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit–cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.

Published
2019

2. A framework for sustained climate assessment in the United States

Author

Moss, RH, Avery, S, Baja, K, Burkett, M, Chischilly, AM, Dell, J, Fleming, PA, Geil, K, Jacobs, K, Jones, A, Knowlton, K, Koh, J, Lemos, MC, Melillo, J, Pandya, R, Richmond, TC, Scarlett, L, Snyder, J, Stults, M, Waple, A, Whitehead, J, Zarrilli, D, Fox, J, Ganguly, A, Joppa, L, Julius, S, Kirshen, P, Kreutter, R, McGovern, A, Meyer, R, Neumann, J, Solecki, W, Smith, J, Tissot, P, Yohe, G, and Zimmerman, R

Subjects
Astronomical and Space Sciences, Atmospheric Sciences, Physical Geography and Environmental Geoscience, Meteorology & Atmospheric Sciences, Atmospheric sciences, Climate change science
Published
2019

3. Evaluating knowledge to support climate action: A framework for sustained assessment. Report of an independent advisory committee on applied climate assessment

Author

Moss, RH, Avery, S, Baja, K, Burkett, M, Chischilly, AM, Dell, J, Fleming, PA, Geil, K, Jacobs, K, Jones, A, Knowlton, K, Koh, J, Lemos, MC, Melillo, J, Pandya, R, Richmond, TC, Scarlett, L, Snyder, J, Stults, M, Waple, AM, Whitehead, J, Zarrilli, D, Ayyub, BM, Fox, J, Ganguly, A, Joppa, L, Julius, S, Kirshen, P, Kreutter, R, McGovern, A, Meyer, R, Neumann, J, Solecki, W, Smith, J, Tissot, P, Yohe, G, and Zimmerman, R

Subjects
North America, Climate prediction, Planning, Policy, Risk assessment, Societal impacts, MD Multidisciplinary
Abstract

As states, cities, tribes, and private interests cope with climate damages and seek to increase preparedness and resilience, they will need to navigate myriad choices and options available to them. Making these choices in ways that identify pathways for climate action that support their development objectives will require constructive public dialogue, community participation, and flexible and ongoing access to science- and experience-based knowledge. In 2016, a Federal Advisory Committee (FAC) was convened to recommend how to conduct a sustained National Climate Assessment (NCA) to increase the relevance and usability of assessments for informing action. The FAC was disbanded in 2017, but members and additional experts reconvened to complete the report that is presented here. A key recommendation is establishing a new nonfederal ‘‘climate assessment consortium’’ to increase the role of state/local/tribal government and civil society in assessments. The expanded process would 1) focus on applied problems faced by practitioners, 2) organize sustained partnerships for collaborative learning across similar projects and case studies to identify effective tested practices, and 3) assess and improve knowledge-based methods for project implementation. Specific recommendations include evaluating climate models and data using user-defined metrics; improving benefit–cost assessment and supporting decision-making under uncertainty; and accelerating application of tools and methods such as citizen science, artificial intelligence, indicators, and geospatial analysis. The recommendations are the result of broad consultation and present an ambitious agenda for federal agencies, state/local/tribal jurisdictions, universities and the research sector, professional associations, nongovernmental and community-based organizations, and private-sector firms.

Published
2019

4. Evaluating Knowledge to Support Climate Action : Framework for Sustained Assessment. Report of an Independent Advisory Committee on Applied Climate Assessment

Author

Moss, R. H., Avery, S., Baja, K., Burkett, M., Chischilly, A. M., Dell, J., Fleming, P. A., Geil, K., Jacobs, K., Jones, A., Knowlton, K., Koh, J., Lemos, M. C., Melillo, J., Pandya, R., Richmond, T. C., Scarlett, L., Snyder, J., Stults, M., Waple, A. M., Whitehead, J., Zarrilli, D., Ayyub, B. M., Fox, J., Ganguly, A., Joppa, L., Julius, S., Kirshen, P., Kreutter, R., Mcgovern, A., Meyer, R., Neumann, J., Solecki, W., Smith, J., Tissot, P., Yohe, G., and Zimmerman, R.

Published
2019

7. CVB Infection and Mechanisms of Viral Cardiomyopathy

Author

Knowlton, K. U., Compans, Richard W., editor, Cooper, Max D., editor, Honjo, Tasuku, editor, Koprowski, Hilary, editor, Melchers, Fritz, editor, Oldstone, Michael B. A., editor, Olsnes, Sjur, editor, Vogt, Peter K., editor, Tracy, Steven, editor, Oberste, M. Steven, editor, and Drescher, Kristen M., editor

Published
2008
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16. Guidelines for Modeling and Reporting Health Effects of Climate Change Mitigation Actions

Author

Hess, JJ, Ranadive, N, Boyer, C, Aleksandrowicz, L, Anenberg, SC, Aunan, K, Belesova, K, Bell, ML, Bickersteth, S, Bowen, K, Burden, M, Campbell-Lendrum, D, Carlton, E, Cisse, G, Cohen, F, Dai, H, Dangour, AD, Dasgupta, P, Frumkin, H, Gong, P, Gould, RJ, Haines, A, Hales, S, Hamilton, I, Hasegawa, T, Hashizume, M, Honda, Y, Horton, DE, Karambelas, A, Kim, H, Kim, SE, Kinney, PL, Kone, I, Knowlton, K, Lelieveld, J, Limaye, VS, Liu, Q, Madaniyazi, L, Martinez, ME, Mauzerall, DL, Milner, J, Neville, T, Nieuwenhuijsen, M, Pachauri, S, Perera, F, Pineo, H, Remais, JV, Saari, RK, Sampedro, J, Scheelbeek, P, Schwartz, J, Shindell, D, Shyamsundar, P, Taylor, TJ, Tonne, C, Van Vuuren, D, Wang, C, Watts, N, West, JJ, Wilkinson, P, Wood, SA, Woodcock, J, Woodward, A, Xie, Y, Zhang, Y, Ebi, KL, Hess, JJ, Ranadive, N, Boyer, C, Aleksandrowicz, L, Anenberg, SC, Aunan, K, Belesova, K, Bell, ML, Bickersteth, S, Bowen, K, Burden, M, Campbell-Lendrum, D, Carlton, E, Cisse, G, Cohen, F, Dai, H, Dangour, AD, Dasgupta, P, Frumkin, H, Gong, P, Gould, RJ, Haines, A, Hales, S, Hamilton, I, Hasegawa, T, Hashizume, M, Honda, Y, Horton, DE, Karambelas, A, Kim, H, Kim, SE, Kinney, PL, Kone, I, Knowlton, K, Lelieveld, J, Limaye, VS, Liu, Q, Madaniyazi, L, Martinez, ME, Mauzerall, DL, Milner, J, Neville, T, Nieuwenhuijsen, M, Pachauri, S, Perera, F, Pineo, H, Remais, JV, Saari, RK, Sampedro, J, Scheelbeek, P, Schwartz, J, Shindell, D, Shyamsundar, P, Taylor, TJ, Tonne, C, Van Vuuren, D, Wang, C, Watts, N, West, JJ, Wilkinson, P, Wood, SA, Woodcock, J, Woodward, A, Xie, Y, Zhang, Y, and Ebi, KL

Abstract

Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers.

Published
2020

17. Guidelines for modeling and reporting health effects of climate change mitigation actions

Author

Hess, J. J., Ranadive, N., Boyer, C., Aleksandrowicz, L., Anenberg, S. C., Aunan, K., Belesova, K., Bell, M. L., Bickersteth, S., Bowen, K., Campbell-Lendrum, D., Burden, M., Carlton, E., Cissé, G., Cohen, F., Dai, H., Dangour, A. D., Dasgupta, P., Frumkin, H., Gong, P., Gould, R. J., Haines, A., Hales, S., Hamilton, I., Hasegawa, T., Hashizume, M., Honda, Y., Horton, D. E., Karambelas, A., Kim, H., Kim, S. E., Kinney, P. L., Knowlton, K., Kone, I., Lelieveld, J., Limaye, V. S., Madaniyazi, L., Liu, Q., Mauzerall, D. L., Martínez, M. E., Milner, J., Neville, T., Nieuwenhuijsen, M., Pachauri, S., Perera, F., Pineo, H., Remais, J. V., Saari, R. K., Scheelbeek, P., Sampedro, J., Schwartz, J., Shindell, D., Shyamsundar, P., Taylor, T. J., Tonne, C., Van Vuuren, D., Wang, D., Watts, N., West, J. J., Wilkinson, P., Woodcock, J, Wood, S. A., Woodward, A., Xie, Y., Zhang, Y., Ebi, K. L., Hess, J. J., Ranadive, N., Boyer, C., Aleksandrowicz, L., Anenberg, S. C., Aunan, K., Belesova, K., Bell, M. L., Bickersteth, S., Bowen, K., Campbell-Lendrum, D., Burden, M., Carlton, E., Cissé, G., Cohen, F., Dai, H., Dangour, A. D., Dasgupta, P., Frumkin, H., Gong, P., Gould, R. J., Haines, A., Hales, S., Hamilton, I., Hasegawa, T., Hashizume, M., Honda, Y., Horton, D. E., Karambelas, A., Kim, H., Kim, S. E., Kinney, P. L., Knowlton, K., Kone, I., Lelieveld, J., Limaye, V. S., Madaniyazi, L., Liu, Q., Mauzerall, D. L., Martínez, M. E., Milner, J., Neville, T., Nieuwenhuijsen, M., Pachauri, S., Perera, F., Pineo, H., Remais, J. V., Saari, R. K., Scheelbeek, P., Sampedro, J., Schwartz, J., Shindell, D., Shyamsundar, P., Taylor, T. J., Tonne, C., Van Vuuren, D., Wang, D., Watts, N., West, J. J., Wilkinson, P., Woodcock, J, Wood, S. A., Woodward, A., Xie, Y., Zhang, Y., and Ebi, K. L.

Abstract

BACKGROUND: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers. OBJECTIVE: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions. METHODS: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies. RESULTS: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting. DISCUSSION: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can info

Published
2020

18. Guidelines for Modeling and Reporting Health Effects of Climate Change Mitigation Actions

Author

Hess, J.J., Ranadive, N., Boyer, C., Aleksandrowicz, L., Anenberg, S.C., Aunan, K., Belesova, K., Bell, M.L., Bickersteth, S., Bowen, K., Burden, M., Campbell-Lendrum, D., Carlton, E., Cissé, G., Cohen, F., Dai, H., Dangour, A.D., Dasgupta, P., Frumkin, H., Gong, P., Gould, R.J., Haines, A., Hales, S., Hamilton, I., Hasegawa, T., Hashizume, M., Honda, Y., Horton, D.E., Karambelas, A., Kim, H., Kim, S.E., Kinney, P.L., Kone, I., Knowlton, K., Lelieveld, J., Limaye, V.S., Liu, Q., Madaniyazi, L., Martinez, M.E., Mauzerall, D.L., Milner, J., Neville, T., Nieuwenhuijsen, M., Pachauri, S., Perera, F., Pineo, H., Remais, J.V., Saari, R.K., Sampedro, J., Scheelbeek, P., Schwartz, J., Shindell, D., Shyamsundar, P., Taylor, T.J., Tonne, C., Van Vuuren, D., Wang, C., Watts, N., West, J.J., Wilkinson, P., Wood, S.A., Woodcock, J., Woodward, A., Xie, Y., Zhang, Y., Ebi, K.L., Hess, J.J., Ranadive, N., Boyer, C., Aleksandrowicz, L., Anenberg, S.C., Aunan, K., Belesova, K., Bell, M.L., Bickersteth, S., Bowen, K., Burden, M., Campbell-Lendrum, D., Carlton, E., Cissé, G., Cohen, F., Dai, H., Dangour, A.D., Dasgupta, P., Frumkin, H., Gong, P., Gould, R.J., Haines, A., Hales, S., Hamilton, I., Hasegawa, T., Hashizume, M., Honda, Y., Horton, D.E., Karambelas, A., Kim, H., Kim, S.E., Kinney, P.L., Kone, I., Knowlton, K., Lelieveld, J., Limaye, V.S., Liu, Q., Madaniyazi, L., Martinez, M.E., Mauzerall, D.L., Milner, J., Neville, T., Nieuwenhuijsen, M., Pachauri, S., Perera, F., Pineo, H., Remais, J.V., Saari, R.K., Sampedro, J., Scheelbeek, P., Schwartz, J., Shindell, D., Shyamsundar, P., Taylor, T.J., Tonne, C., Van Vuuren, D., Wang, C., Watts, N., West, J.J., Wilkinson, P., Wood, S.A., Woodcock, J., Woodward, A., Xie, Y., Zhang, Y., and Ebi, K.L.

Abstract

Background: Modeling suggests that climate change mitigation actions can have substantial human health benefits that accrue quickly and locally. Documenting the benefits can help drive more ambitious and health-protective climate change mitigation actions; however, documenting the adverse health effects can help to avoid them. Estimating the health effects of mitigation (HEM) actions can help policy makers prioritize investments based not only on mitigation potential but also on expected health benefits. To date, however, the wide range of incompatible approaches taken to developing and reporting HEM estimates has limited their comparability and usefulness to policymakers. Objective: The objective of this effort was to generate guidance for modeling studies on scoping, estimating, and reporting population health effects from climate change mitigation actions. Methods: An expert panel of HEM researchers was recruited to participate in developing guidance for conducting HEM studies. The primary literature and a synthesis of HEM studies were provided to the panel. Panel members then participated in a modified Delphi exercise to identify areas of consensus regarding HEM estimation. Finally, the panel met to review and discuss consensus findings, resolve remaining differences, and generate guidance regarding conducting HEM studies. Results: The panel generated a checklist of recommendations regarding stakeholder engagement: HEM modeling, including model structure, scope and scale, demographics, time horizons, counterfactuals, health response functions, and metrics; parameterization and reporting; approaches to uncertainty and sensitivity analysis; accounting for policy uptake; and discounting. Discussion: This checklist provides guidance for conducting and reporting HEM estimates to make them more comparable and useful for policymakers. Harmonization of HEM estimates has the potential to lead to advances in and improved synthesis of policy-relevant research that can info

Published
2020

26. A Framework for Sustained Climate Assessment in the United States A Framework for Sustained Climate Assessment in the United States

Author

Moss, RH, Avery, S, Baja, K, Burkett, M, Chischilly, AM, Dell, J, Fleming, PA, Geil, K, Jacobs, K, Jones, A, Knowlton, K, Koh, J, Lemos, MC, Melillo, J, Pandya, R, Richmond, TC, Scarlett, L, Snyder, J, Stults, M, Waple, A, Whitehead, J, Zarrilli, D, Fox, J, Ganguly, A, Joppa, L, Julius, S, Kirshen, P, Kreutter, R, McGovern, A, Meyer, R, Neumann, J, Solecki, W, Smith, J, Tissot, P, Yohe, G, and Zimmerman, R

Subjects
Climate Action, Meteorology & Atmospheric Sciences, Astronomical and Space Sciences, Physical Geography and Environmental Geoscience, Atmospheric Sciences
Published
2019

27. Ch. 9: Human Health. Climate Change Impacts in the United States: The Third National Climate Assessment

Author

Luber, G., primary, Knowlton, K., additional, Balbus, J., additional, Frumkin, H., additional, Hayden, M., additional, Hess, J., additional, McGeehin, M., additional, Sheats, N., additional, Backer, L., additional, Beard, C. B., additional, Ebi, K. L., additional, Maibach, E., additional, Ostfeld, R. S., additional, Wiedinmyer, C., additional, Zielinski-Gutiérrez, E., additional, and Ziska, L., additional

Published
2014
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35. A fecal test for assessing phosphorus overfeeding on dairy farms : evaluation using extensive farm data

Author

Dou, Z., Ramberg, C. F., Chapuis Lardy, Lydie, Toth, J. D., Wu, Z., Chase, L. E., Kohn, R. A., Knowlton, K. F., and Ferguson, J. D.

Subjects
fecal P test, dairy farm, P overfeeding, assessment
Abstract

Managing P on dairy farms requires the assessment and monitoring of P status of the animals so that potential overfeeding may be minimized. Numerous published studies have demonstrated that for lactating dairy cows, increasing P concentrations in diets led to greater P excretion in feces. More recent work reported that inorganic P (P-i) in 0.1% HCl extracts of feces (fecal extract P-i, g/kg) closely reflects dietary P changes. This has led to the proposal that 0.1% HCl fecal extract P-i may serve as an indicator of the animal's P status (adequate or excessive) when compared with a benchmark value. Here, we present the results of an extensive evaluation of the proposed fecal P indicator test. With samples (n = 575) from >90 farms, fecal total P (TP, g/kg) and fecal extract P were positively correlated with dietary P (X, g/kg): TP = 1.92X - 0.17 (R-2 = 0.36); fecal extract P = 1.82X - 2.54 (R-2 = 0.46). Fecal extract P was responsive to dietary P changes, whereas the remaining P, calculated as TP minus fecal extract P, was not. A provisional benchmark value of fecal extract P representing near-adequate P status was set at 4.75 g/kg. Assessment of the farm data using the benchmark indicated that 316 out of 575 data points were associated with possible P overfeeding. Advantages of the fecal-based test over feed-based analysis to assess P status are discussed. The fecal extract P method is a simple and practical test that can be used as an assessment tool for helping dairy producers improve P management and reduce their environmental footprint.

Published
2010

37. Air Quality in Future Decades – Determining the Relative Impacts of Changes in Climate, Emissions, Global Atmospheric Composition, and Regional Land Use

Author

Hogrefe, C., primary, Lynn, B., additional, Solecki, B., additional, Cox, J., additional, Small, C., additional, Knowlton, K., additional, Rosenthal, J., additional, Goldberg, R., additional, Rosenzweig, C., additional, Civerolo, K., additional, Ku, J.-Y., additional, Gaffin, S., additional, and Kinney, P. L., additional

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41. Invited review: Sustainability of the US dairy industry

Author

von Keyserlingk, M. A. G., Martin, N. P., Kebreab, E., Knowlton, K. F., Grant, R.J., Stephenson, M., II, Sniffen, C.J., Harner, J.P., III, Wright, A.D., Smith, S.I., von Keyserlingk, M. A. G., Martin, N. P., Kebreab, E., Knowlton, K. F., Grant, R.J., Stephenson, M., II, Sniffen, C.J., Harner, J.P., III, Wright, A.D., and Smith, S.I.

Abstract

The US dairy industry has realized tremendous improvements in efficiencies and milk production since the 1940s. During this time, farm and total cow numbers have decreased and average herd size has increased. This intensification, combined with the shift to a largely urban public, has resulted in increased scrutiny of the dairy industry by social and environmental movements and increased concern regarding the dairy industry’s sustainability. In response to these concerns, a group of scientists specializing in animal welfare, nutrient management, greenhouse gas emissions, animal science, agronomy, agricultural engineering, microbiology, and economics undertook a critical review of the US dairy industry. Although the US dairy system was identified as having significant strengths, the consensus was that the current structure of the industry lacks the resilience to adapt to changing social and environmental landscapes. We identified several factors affecting the sustainability of the US dairy industry, including climate change, rapid scientific and technological innovation, globalization, integration of societal values, and multidisciplinary research initiatives. Specific challenges include the westward migration of milk production in the United States (which is at odds with projected reductions in precipitation and associated limitations in water availability for cattle and crops), and the growing divide between industry practices and public perceptions, resulting in less public trust. Addressing these issues will require improved alignment between industry practices and societal values, based upon leadership from within the industry and sustained engagement with other interested participants, including researchers, consumers, and the general public.

Published
2013

42. Mechanical Translation

Author

Knowlton, K. C., Percival, W. K., Satterthwait, A. C., Knowlton, K. C., Percival, W. K., and Satterthwait, A. C.

Abstract

Contains reports on three research projects., National Science Foundation (Grant G-24047)

Published
2010

45. The alpha 1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy

Author

Knowlton, K. U., Michel, M. C., Itani, M., Shubeita, H. E., Ishihara, K., Brown, J. H., Chien, K. R., and Other departments

Abstract

alpha 1-Adrenergic agonists induce a hypertrophic phenotype in cultured neonatal rat ventricular myocytes. Quantifiable markers of this phenotype include stimulation of phosphoinositide hydrolysis, transcriptional induction of atrial natriuretic factor (ANF) gene expression, and an increase in myocardial cell size. The aim of the present work was to determine which alpha 1-adrenergic receptor subtype mediates the acquisition of these parameters of myocardial cell hypertrophy. Phosphoinositide hydrolysis is inhibited by low concentrations of 5-methylurapidil (log Ki = -8.7) and (+)-niguldipine (log Ki = -10.6). The alpha-adrenergic receptor-induced increase in transcriptional activation of an ANF luciferase reporter gene is inhibited over the same range of concentrations of 5-methylurapidil (log Ki = -8.2) and (+)-niguldipine (log Ki = -11.2) that inhibit phosphoinositide hydrolysis. In addition, the increase in cell size that accompanies alpha-adrenergic receptor stimulation of cultured ventricular myocytes is blocked by similar concentrations of 5-methylurapidil (log Ki = -8.0) and (+)-niguldipine (log Ki = -10.6). In contrast, treatment with the alpha 1B selective antagonist chlorethylclonidine at a concentration of 10 microM had no effect on the adrenergically mediated induction of ANF luciferase reporter gene expression or the adrenergically induced increase in myocardial cell size. These findings demonstrate that pharmacologically identifiable alpha 1A-adrenergic receptors mediate not only the early effects of alpha 1-adrenergic stimulation such as phosphoinositide hydrolysis, but that they activate the signaling pathways that control transcriptional induction of the ANF luciferase reporter gene and an increase in myocardial cell size. Studies using alpha 1-adrenergic receptor cDNAs to delineate and alter the direct interaction of this receptor subtype with proximal signaling molecules, e.g. GTP binding proteins, should provide a powerful means of assessing their role in the induction of the molecular and morphologic parameters of myocardial cell hypertrophy

Published
1993

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