Renal Flashcards
(35 cards)
Explain the mechanisms underlying hypertension
explain how reduced nitric oxide levels can induce hypertension
explain the
novel treatments for hypertension based on the L-arginine-nitric pathway
To define heart failure with preserved ejection fraction and heart failure with reduced ejection fraction
explain the mechanisms which link heart failure with renal failure
overactivation of the sympathetic nerves and overactivation of the renin angiotensin system
increase oxidative stress and reduce nitric oxide bioavailability contributing to kidney fibrosis and inflammation which in turn lead to a decline in glomerular filtration rate (GFR) in heart failure
explain the pathogenic role of nitric oxide deficiency in development of heart failure related renal disease
Explain recent research in the field of cardiorenal disease
Explain the role of oxidative stress in cardiorenal syndrome
Explain how we can use antioxidants to target oxidative stress in cardiorenal
syndrome
Explain the effects of serelaxin (a drug from Novartis which can reduce oxidative stress) on cardiorenal syndrome
Explain the role of the renin angiotensin system in cardiorenal syndrome
What are the mechanisms of obesity-induced hypertension
Visceral obesity leads to an increase in Leptin, RAAS activation, renal compression, and metabolic disorders, which then leads to SNS activation, and an increase in renal sodium reabsorption, which leads to an increase in blood pressure causing hypertension followed by chronic kidney disease. The Glomerular also undergoes hyperfiltration which contributes to the development of chronic kidney disease
What are a few functions of Nitric Oxide (NO)
- NO is a vasodilator
- NO plays a central role in regulating extracellular fluid homeostasis
- NO plays a key role in the regulation of renal blood flow and blood pressure
- Reduction in NO bioavailability can lead to hypertension and kidney disease
What are the 3 ways to increase nitric oxide bioavailability in the cardiovascular system
- First compounds such as L-arginine, L-citrulline, and arginase inhibitors increase substrates and cofactors necessary for NO synthase activity.
- blocking endogenous inhibitory pathways will increase NO bioavailability. ACE inhibitors, Ang 2, receptor 1 blockers and NADPH oxidase inhibitors will reduce the formation of superoxide thereby limiting NO scavenging and peroxynitrite generation increasing NO bioavailability
- statins, polyphenols, nebivolol, and corticosteroids are able to increase endothelial NOS activity mainly through phosphorylation. Inhibitors of endogenous NOS inhibitors also increase endothelial NOS. Finally, NO can be directly inhaled or can be derived from organic nitrates.
How does the use of organic nitrates increase nitric oxide
Upon nitrate bioactivation, NO stimulates soluble guanylyl cyclase, increases cyclic 3 and 5 cGMP that activates cGMP-dependent protein kinase, and subsequently decreases intracellular calcium levels. The decreased calcium levels reduce the contractility of myosin/actin filaments via inhibition of the myosin light chain phosphorylation and therefore cause vasorelaxation
Explain what occurs when NO gas is inhaled but why it is not a long-term solution
inhaled NO gas clearly vasodilates the pulmonary circulation and improves ventilation–perfusion matching and oxygenation in patients with acute lung injury, but this response is transient, only lasting a few days.
L-arginine as a hypertension cure
Augmented endothelial L-arginine transport can ameliorate obesity-induced hypertension
Anti-hypertensive effects of endothelial L-arginine transport are mediated by preserving NO bioavailability. This inturn buffers the activity of the sympathetic nervous system and renal renin-angiotensin system (RAS).
What did the research find about Endothelial CAT1 overexpression
Endothelial CAT1 overexpression can ameliorate obesity-induced
hypertension by preserving NO levels and thereby buffering the actions of the sympathetic nervous system.
Thus, L-Arg transport is likely to be a potential new treatment target in
obesity-dependent hypertension.
What is the difference between heart failure with Preserved ejection fraction vs Reduced ejection fraction
- HF Preserved ejection fraction is Diastolic heart failure, where the walls are thickened and stiff resulting in the heart struggling to fill
- HF Reduced ejection fraction is Systolic heart failure, where the walls are thin and dilated resulting in the heart struggling to pump
What are the systemic factors that contribute to cardiorenal syndrome
- Diabetes
- hypertension
- obesity
-metabolic syndrome - amyloidosis
mechanisms underlying the relationship between heart failure (HF) and renal dysfunction
- HF causes the sympathetic nervous system to activate the RAAS causing a few of the following, a decrease in cardiac output resulting in a decrease in renal blood flow / GFR resulting in renal dysfunction. HF also causes activation of RAAS causing an increase in oxidative stress and a decrease in nitric oxide, leading to inflammation and fibrosis resulting in renal dysfunction
what are mechanisms underlying the relationship between heart failure (HF) and renal dysfunction
overactivation of the sympathetic nerves and overactivation of the renin angiotensin system
increase oxidative stress and reduce nitric oxide bioavailability contributing to kidney fibrosis and inflammation which in turn lead to a decline in glomerular filtration rate (GFR) in heart failure
How does reduced nitric oxide impact kidney function?
- reduce renal perfusion
- Impair sodium and water reabsorption
- Reduce glomerular filtration rate
- Impair tubuloglomerular feedback mechanism
- Impair myogenic response
- Enhance renal vasoconstrictor responses to renal sympathetic nerve activity, thereby leading to renal ischemia
- Augment the vasoconstrictor activity of the renin angiotensin aldosterone system (RAAS)
What are the actions of ANG II
Actions of ANG II:
* potent vasoconstrictor – nitric oxide
counteracts this effect
* activates sodium reabsorption
* stimulates aldosterone production
* Stimulates ADH release
