- Assistant Professor, Physiology
- Assistant Professor, Surgery
- Member of the Graduate Faculty
- Ph.D. Pharmacology and Toxicology
- Michigan State University, East Lansing, Michigan, United States
- The role of inflammatory mediators in hypertensive remodeling of cerebral arteries : focus on perivascular macrophages, matrix metalloproteinases and tumor necrosis factor-alpha
- M.S. Cell and Structural Biology
- Campinas State University, Campinas, Sao Paulo, Brazil
- Chronic ethanol intake promotes double gluthatione S-transferase/transforming growth factor-alpha-positive hepatocellular lesions in male Wistar rats
- B.S. Biological Sciences
- Sao Paulo State University, Botucatu, Sao Paulo, Brazil
- University of Nevada Reno School of Medicine (2014 - 2018)
- Michigan State University, East Lansing, Michigan (2013 - 2014)
- Michigan State University, East Lansing, Michigan (2008 - 2009)
No activities entered.
Cellular+Molecular PsioPSIO 503 (Fall 2021)
Honors ThesisPSIO 498H (Fall 2021)
Physiology SeriesPSIO 696A (Fall 2021)
ResearchPS 900 (Fall 2021)
Rsrch Meth Psio SciPS 700 (Fall 2021)
ResearchPS 900 (Summer I 2021)
Human PhysiologyPSIO 603A (Spring 2021)
Physiology SeriesPSIO 696A (Spring 2021)
Physiology Student ForumPS 696C (Spring 2021)
Physiology/Biomed EngrBME 511 (Spring 2021)
Physiology/Biomed EngrPSIO 511 (Spring 2021)
ResearchPS 900 (Spring 2021)
ThesisPS 910 (Spring 2021)
Cellular+Molecular PsioPSIO 503 (Fall 2020)
Directed ResearchMCB 792 (Fall 2020)
Physiology SeriesPSIO 696A (Fall 2020)
Physiology Student ForumPS 696C (Fall 2020)
ResearchPS 900 (Fall 2020)
Rsrch Meth Psio SciPS 700 (Fall 2020)
Directed ResearchMCB 792 (Spring 2020)
Directed ResearchPSIO 492 (Spring 2020)
Honors ThesisPSIO 498H (Spring 2020)
Physiology SeriesPSIO 696A (Spring 2020)
Physiology Student ForumPS 696C (Spring 2020)
Physiology/Biomed EngrBME 511 (Spring 2020)
Physiology/Biomed EngrPSIO 511 (Spring 2020)
ResearchPS 900 (Spring 2020)
Cellular+Molecular PsioPSIO 503 (Fall 2019)
Honors ThesisPSIO 498H (Fall 2019)
Introduction to ResearchMCB 795A (Fall 2019)
Physiology SeriesPSIO 696A (Fall 2019)
Rsrch Meth Psio SciPS 700 (Fall 2019)
- Pires, P. (2018). Cannabinoids during ischemic strokes: friends or foes?. American Journal of Physiology-Heart and Circulatory Physiology.
- Pires, P. (2018). Nanoscale remodeling of ryanodine receptor cluster size underlies cerebral microvascular dysfunction in Duchenne muscular dystrophy. Proceedings of the National Academy of Sciences.
- Pires, P. (2018). Neuroprotective effects of TRPA1 channels in the cerebral endothelium following ischemic stroke. eLife.
- Pires, P. W., McClain, J. L., Hayoz, S. F., & Dorrance, A. M. (2018). Mineralocorticoid receptor antagonism prevents obesity-induced cerebral artery remodeling and reduces white matter injury in rats. Microcirculation (New York, N.Y. : 1994), 25(5), e12460.More infoMidlife obesity is a risk factor for dementia development. Obesity has also been linked to hyperaldosteronism, and this can be modeled in rats by high fat (HF) feeding from weaning. Aldosterone, or activation of the mineralocorticoid receptor (MR) causes cerebrovascular injury in lean hypertensive rats. We hypothesized that rats fed a HF diet would show inward middle cerebral artery (MCA) remodeling that could be prevented by MR antagonism. We further proposed that the cerebral artery remodeling would be associated with white mater injury.
- Pires, P. (2017). Microtubule structures underlying the sarcoplasmic reticulum support peripheral coupling sites to regulate smooth muscle contractility. Science Signaling.
- Pires, P. (2017). The angiotensin II receptor type 1b is the primary sensor of intraluminal pressure in cerebral artery smooth muscle cellS. The Journal of Physiology.
- Pires, P. W., & Earley, S. (2017). Redox regulation of transient receptor potential channels in the endothelium. Microcirculation (New York, N.Y. : 1994), 24(3).More infoROS and RNS are important mediators of signaling pathways in the endothelium. Specific members of the TRP superfamily of cation channels act as important Ca influx pathways in endothelial cells and are involved in endothelium-dependent vasodilation, regulation of barrier permeability, and angiogenesis. ROS and RNS can modulate the activity of certain TRP channels mainly by modifying specific cysteine residues or by stimulating the production of second messengers. In this review, we highlight the recent literature describing redox regulation of TRP channel activity in endothelial cells as well as the physiological importance of these pathways and implication for cardiovascular diseases.
- Matin, N., Pires, P. W., Garver, H., Jackson, W. F., & Dorrance, A. M. (2016). DOCA-salt hypertension impairs artery function in rat middle cerebral artery and parenchymal arterioles. Microcirculation (New York, N.Y. : 1994), 23(7), 571-579.More infoChronic hypertension induces detrimental changes in the structure and function of surface cerebral arteries. Very little is known about PAs, which perfuse distinct neuronal populations in the cortex and may play a role in cerebrovascular disorders. We investigated the effect of DOCA-salt induced hypertension on endothelial function and artery structure in PAs and MCAs.
- Pires, P. W., & Earley, S. (2016). A TRPC3 signalling complex promotes cerebral artery remodelling during hypertension. Cardiovascular research, 109(1), 4-5.
- Pires, P. W., & Earley, S. (2016). No Static at All: Tuning Into the Complexities of Ca2+ Signaling in the Endothelium. Circulation research, 118(7), 1042-4.
- Pires, P. W., Dabertrand, F., & Earley, S. (2016). Isolation and Cannulation of Cerebral Parenchymal Arterioles. Journal of visualized experiments : JoVE.More infoIntracerebral parenchymal arterioles (PAs), which include parenchymal arterioles, penetrating arterioles and pre-capillary arterioles, are high resistance blood vessels branching out from pial arteries and arterioles and diving into the brain parenchyma. Individual PA perfuse a discrete cylindrical territory of the parenchyma and the neurons contained within. These arterioles are a central player in the regulation of cerebral blood flow both globally (cerebrovascular autoregulation) and locally (functional hyperemia). PAs are part of the neurovascular unit, a structure that matches regional blood flow to metabolic activity within the brain and also includes neurons, interneurons, and astrocytes. Perfusion through PAs is directly linked to the activity of neurons in that particular territory and increases in neuronal metabolism lead to an augmentation in local perfusion caused by dilation of the feed PA. Regulation of PAs differs from that of better-characterized pial arteries. Pressure-induced vasoconstriction is greater in PAs and vasodilatory mechanisms vary. In addition, PAs do not receive extrinsic innervation from perivascular nerves - innervation is intrinsic and indirect in nature through contact with astrocytic endfeet. Thus, data regarding contractile regulation accumulated by studies using pial arteries does not directly translate to understanding PA function. Further, it remains undetermined how pathological states, such as hypertension and diabetes, affect PA structure and reactivity. This knowledge gap is in part a consequence of the technical difficulties pertaining to PA isolation and cannulation. In this manuscript we present a protocol for isolation and cannulation of rodent PAs. Further, we show examples of experiments that can be performed with these arterioles, including agonist-induced constriction and myogenic reactivity. Although the focus of this manuscript is on PA cannulation and pressure myography, isolated PAs can also be used for biochemical, biophysical, molecular, and imaging studies.
- Pires, P. (2015). TRPs in the kidney - location, location, location. Acta Physiologica.
- Pires, P. (2015). Unitary TRPV3 channel Ca2+ influx events elicit endothelium-dependent dilation of cerebral parenchymal arterioles. American Journal of Physiology-Heart and Circulatory Physiology.
- Pires, P. (2015). Vascular biology: Localized TRPA1 channel Ca2+ signals stimulated by reactive oxygen species promote cerebral artery dilation. Science Signaling.
- Pires, P. (2014). The effects of obesity on the cerebral vasculature. Current Vascular Pharmacology.
- Pires, P. (2014). Tumor necrosis factor-α inhibition attenuates middle cerebral artery remodeling but increases cerebral ischemic damage in hypertensive rats. American Journal of Physiology - Heart and Circulatory Physiology.
- Pires, P. (2013). Improvement in middle cerebral artery structure and endothelial function in stroke-prone spontaneously hypertensive rats after macrophage depletion. Microcirculation.
- Pires, P. (2013). The effects of hypertension on the cerebral circulation. American Journal of Physiology - Heart and Circulatory Physiology.
- Pires, P. (2012). Direct regulation of blood pressure by smooth muscle cell mineralocorticoid receptors. Nature Medicine.
- Pires, P. (2012). The development of hypertension and hyperaldosteronism in a rodent model of life-long obesity. Endocrinology.
- Pires, P. (2011). Doxycycline, a matrix metalloprotease inhibitor, reduces vascular remodeling and damage after cerebral ischemia in stroke-prone spontaneously hypertensive rats. American Journal of Physiology - Heart and Circulatory Physiology.
- Pires, P. (2010). Effects of gestational and lactational fenvalerate exposure on immune and reproductive systems of male rats. Journal of Toxicology and Environmental Health - Part A: Current Issues.
- Pires, P. (2010). Tempol, a superoxide dismutase mimetic, prevents cerebral vessel remodeling in hypertensive rats. Microvascular Research.
- Pires, P. (2009). Metalloproteinases 2 and -9 activity during promotion and progression stages of rat liver carcinogenesis. Journal of Molecular Histology.
- Pires, P. (2008). Chronic ethanol intake promotes double gluthatione S-transferase/transforming growth factor-α-positive hepatocellular lesions in male Wistar rats. Cancer Science.
- Pires, P. (2007). Liver lesions produced by aflatoxins in Rana catesbeiana (bullfrog). Ecotoxicology and Environmental Safety.
- Peters, E. C., Ayon, R. J., & Pires, P. W. (2020, April). Amyloid-β(1-42) Inhibits Ca2+ Transients Induced by N-Methyl-D-Aspartate Receptor in The Cerebral Vasculature. Experimental Biology. San Diego, CA: American Physiological Society.More infoEndothelium-dependent dilation of cerebral arteries, a process dependent on transient increases in intracellular calcium (Ca2+), contributes to neurovascular coupling (NVC), which is altered in cerebral amyloid angiopathy (CAA).The N-methyl-D-aspartate receptor (NMDAR), a nonselective cation channel with high Ca2+ permeability, has been shown to mediate endothelium-dependent dilation in cerebral arteries. NMDAR activity is reduced by amyloid-β, which accumulates around the cerebral vasculature during CAA. We hypothesized that amyloid-β impairs NMDAR-induced Ca2+ transients in endothelial cells of cerebral arteries, which impairs endothelium-mediated dilation in mice. All animal experiments were approved by the University of Arizona IACUC. Data are means ± SEM, both in male and female mice (no sex differences were observed). Cerebral arteries isolated from mice expressing the genetically-encoded calcium indicator GCaMP8 in endothelial cells (cdh5:Gcamp8) were prepared en face for time-lapse imaging of endothelial Ca2+ transients induced by NMDAR activation. In fields of view that displayed Ca2+ transients, we found that the NMDAR agonist NMDA (1 µM) increased the frequency of endothelial Ca2+ transients compared to baseline (0.22 ± 0.06 vs 0.58 ± 0.15 Hz, baseline vs NMDA, n = 10 and 13 fields of view from at least 3 mice, p < 0.05, one way ANOVA). Pre-incubation of preparations with the NMDAR antagonist D-AP5 (10 µM) prevented NMDA induction of endothelial cell Ca2+ transients (frequency: 0.14 ± 0.05, n = 10 fields of view, p < 0.05 vs NMDA, one-way ANOVA). These data suggest that endothelial NMDAR Ca2+ transients can be stimulated in cerebral arteries via NMDA. We then tested whether the peptide amyloid-β(1-42), commonly found in CAA, blunted NMDAR-elicited Ca2+ transients. Cerebral artery preparations were incubated for 30 minutes with 5 µM amyloid-β(1-42), then exposed to NMDA. Our preliminary data suggests that pre-incubation of preparations with amyloid-β blunts NMDA-dependent induction of endothelial cell Ca2+ transients (0.21 ± 0.04, n = 10 fields of view, p < 0.05 vs NMDA, one-way ANOVA). In order to evaluate the effects of amyloid-β on dilation of cerebral arterioles, we then performed ex vivo pressure myography experiments with cerebral parenchymal arterioles from a mouse model of familial Alzheimer’s disease without aging (5x-FAD) or wildtype littermates. Our preliminary results suggest that NMDA-elicited dilation of parenchymal arterioles may be impaired in 5x-FAD mice (vasodilation (%): 11.06 ± 0.78 vs 6.21 ± 2.09, wildtype vs 5x-FAD, n = 3 arterioles from 3 mice, p = 0.067, two-tailed Student’s t-test). These preliminary data suggest that NMDA receptors in the cerebrovascular endothelium of wildtype mice mediate arteriolar dilation via an increase in Ca2+ transients. Further, amyloid-β may impair the activity of endothelial NMDA receptors and thus contribute to neurovascular dysfunction via impaired arteriolar dilation in individuals with CAA.