ArticlePloS one2013
Phosphodiesterase 5 attenuates the vasodilatory response in renovascular hypertension.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 29 citations in OpenAlex.
- Exploring the Multifaceted Potential of Sildenafil in Medicine.Medicina (Kaunas, Lithuania) · 2023Review
- The differential roles of the two NO-GC isoforms in adjusting airway reactivity.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Age Impairs Soluble Guanylyl Cyclase Function in Mouse Mesenteric Arteries.International journal of molecular sciences · 2021Article
- Angiotensin-converting enzyme 2 (ACE2): COVID 19 gate way to multiple organ failure syndromes.Respiratory physiology & neurobiology · 2021Review
- Type 5 phosphodiesterase (PDE5) and the vascular tree: From embryogenesis to aging and disease.Mechanisms of ageing and development · 2020Review
- The phosphodiesterase 5 inhibitor tadalafil has renoprotective effects in a rat model of chronic kidney disease.Physiological reports · 2020Article
- Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review.Journal of clinical medicine · 2020Review
- The Impact of the Nitric Oxide (NO)/Soluble Guanylyl Cyclase (sGC) Signaling Cascade on Kidney Health and Disease: A Preclinical Perspective.International journal of molecular sciences · 2018Review
- Impact of the NO-Sensitive Guanylyl Cyclase 1 and 2 on Renal Blood Flow and Systemic Blood Pressure in Mice.International journal of molecular sciences · 2018Article
- Role of Phosphodiesterase 5 and Cyclic GMP in Hypertension.Current hypertension reports · 2016Review
- PDE5 Exists in Human Neurons and is a Viable Therapeutic Target for Neurologic Disease.Journal of Alzheimer's disease : JAD · 2016Article
- Inhibition of PDE5 Restores Depressed Baroreflex Sensitivity in Renovascular Hypertensive Rats.Frontiers in physiology · 2016Article
- Sildenafil ameliorates oxidative stress and DNA damage in the stenotic kidneys in mice with renovascular hypertension.Journal of translational medicine · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
NO/cGMP signaling plays an important role in vascular relaxation and regulation of blood pressure. The key enzyme in the cascade, the NO-stimulated cGMP-forming guanylyl cyclase exists in two enzymatically indistinguishable isoforms (NO-GC1, NO-GC2) with NO-GC1 being the major NO-GC in the vasculature. Here, we studied the NO/cGMP pathway in renal resistance arteries of NO-GC1 KO mice and its role in renovascular hypertension induced by the 2-kidney-1-clip-operation (2K1C). In the NO-GC1 KOs, relaxation of renal vasculature as determined in isolated perfused kidneys was reduced in accordance with the marked reduction of cGMP-forming activity (80%). Noteworthy, increased eNOS-catalyzed NO formation was detected in kidneys of NO-GC1 KOs. Upon the 2K1C operation, NO-GC1 KO mice developed hypertension but the increase in blood pressures was not any higher than in WT. Conversely, operated WT mice showed a reduction of cGMP-dependent relaxation of renal vessels, which was not found in the NO-GC1 KOs. The reduced relaxation in operated WT mice was restored by sildenafil indicating that enhanced PDE5-catalyzed cGMP degradation most likely accounts for the attenuated vascular responsiveness. PDE5 activation depends on allosteric binding of cGMP. Because cGMP levels are lower, the 2K1C-induced vascular changes do not occur in the NO-GC1 KOs. In support of a higher PDE5 activity, sildenafil reduced blood pressure more efficiently in operated WT than NO-GC1 KO mice. All together our data suggest that within renovascular hypertension, cGMP-based PDE5 activation terminates NO/cGMP signaling thereby providing a new molecular basis for further pharmacological interventions.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.