Renal - Rajapake L1: NO and hypertension 1. What % of hypertension cases are caused by underlying obesity? 2. Mechanisms underpinning hypertension Visceral obesity + Leptin/ POMC SNS activation RAAS and MR activation Renal compression Renal Na* reabsorption 1 Metabolic disorders · Insulin resistance · Glucose intolerance · Dyslipidemia · Inflammation Lipotoxicity Afferent arteriolar resistance - Macula Densa Feedback Impaired renal-pressure natriuresis Blood pressure + ++ Glomerular hyperfiltration Chronic Kidney Disease 1. What three areas of this diagram does NO target? Research developments in hypertension 1. What are the cellular mechanisms through which NO ameliorates hypertension? 2. How NO can induce hypertension L-arg novel treatments for hypertension 1. Why does NO inhalation have reduced efficancy ticlue: think of L-argffi 2. How do L-arg transport and NO levels compare between obese and control people? 3. What changes in blood pressure is reduced CAT-1 expression associated with? Inducing CAT-1: . Restored tireducedffi SNS activity in fat mice · Restored tireducedffi angiotensin II in fat mice o Angiotensin II decreases L-arg transport . Restored tiincreasedffi NO bioavailability in fat mice · Restored tidecreasedffi hypertension in fat mice Conclusions: 1. How does high fibre diet link to [NO] L2: Cardiorenal Syndrome & NO 1. Define cardiorenal syndrome 2. Is there effective treatment for CRS? 3. What systemic factors contribute to CRS tiClue: DOHMAffi 4. True or false: only HFpEF is associated with renal dysfunction?
5. What are the eGFRs for stage 1-5 CKD? 6. What does EPO do? a. What happens to EPO when the kidneys are damaged? What are the downstream consequences of that ticlue: bone barrowffi. 7. What are the three diagnostic markers in CKD? ticlue: GFR, Blood Urea Nitrogen, Hemoglobinffi a. What are two other possible markers for CKD ff. Write out the flow chart of how heart failure results in renal dysfunction 9. How does reduced NO impair kidney function ti7ffi 10. What are the actions of angiotensin II ti4ffi 11. How are ACE inhibitors used to treat kidney disease? How do they impact NO levels? 12. What is the relationship between NO bioavailability and Ang II? ticlue: see-sawffi 13. True or false: NO bioavailability is increased in HF 14. Why can't L-arg be administered/supplemented to increase NO? 15. Do HF patients have the same CAT-1 expression as controls? a. What does this say about L-arg transport in HF patients? DCM mouse = mouse mimicking HF HFCAT1 mouse = HF mouse with CAT-1 genes CAT-1 transgenic mouse · Tubulointerstitial fibrosis · Glomerular fibrosis · Renal function tialbumin:creatineffi · Inflammatory gene expression · Pro-fibrotic gene pai-1 · Plasma nitrate and nitrite levels Heart failure SNS RAAS Cardiac output Oxidative stress, nitric oxide Inflammation, fibrosis Renal blood flow, GFR Progressive renal dysfunction L3 - cardiorenal syndrome & oxidative stress 1. Deficiency in tiantioxidant speciesffi is associated with HF and CKD 2. What is NAC a precursor for? 3. What does administration of NAC do? 4. What were the effects of NAC on: a. Tubulointerstial fibrosis b. Glomerular fibrosis c. Collagen Type d.