1. Blood pressure (BP) A constant flow of blood is necessary to transport oxygen to the cells of the body The arteries maintain an average blood pressure of around 90 mmHg This helps push the blood from the arteries into the capillaries In the capillaries, oxygen transfers from the blood to the cells

2. Systole and Diastole The arteries fluctuate between a state of systole and diastole In systole, the pressure in the arteries increases as the heart pumps blood into the arterial system As the pressure increases, the elastic walls of the arteries stretch This can be felt as a pulse in certain arteries

3. Systole and Diastole In diastole, the recoil of the elastic arteries forces blood out of the arterial system into the capillaries The pressure in the arteries falls as blood leaves the system Minimum diastolic pressure is typically 70-80 mmHg Maximum systolic pressure is typically 110-120 mmHg

4. Artery in systole and diastole

5. Here is a graph of changes in arterial BP Note that there is always pressure in the arteries, never much below 70 – 80 mmHg

6. Put another way Think of the arterial system as a long balloon that you are trying to blow up. Unfortunately the balloon has an hole in the end… However, as long as the puff going in is equal to the air leaking out, the balloon remains inflated (BP is maintained)

7. BP Formula Blood pressure depends on cardiac output (CO) and systemic vascular resistance (SVR) BP = CO x SVR* Cardiac output depends on heart rate and stroke volume CO = HR x SV* *SVR = total resistance of arterioles to flow of blood *SV = the amount of blood pumped by the heart each cycle

8. Control of Blood Pressure The body responds quickly to falls in arterial pressure This immediate response is to increase cardiac output (CO) and systemic vascular resistance (SVR) Sympathetic activity causes vasoconstriction. This increases SVR

9. Vasoconstriction

10. Control of Blood Pressure Sympathetic activity causes an increase in both heart rate and stroke volume These both increase cardiac output CO = HR x SV Both SVR and CO have now increased so BP will increase BP = CO x SVR

11. Put another way If your balloon was losing pressure, there are two actions you can take… 1. put more puff into the balloon (increase CO) 2. let less air out of the balloon by pinching the end (increase SVR)

12. Baroreceptors How does the body know that there has been a fall in blood pressure? Baroreceptors on the aorta and carotid artery respond to falls in BP They send signals to the cardiovascular centre in the brain stem medulla The medulla sends signals along the sympathetic nerves to the arterioles and heart, increasing SVR and cardiac output

13. A fall in BP triggers vasoconstriction

14. A fall in BP triggers an increase in cardiac output

15. Summary A drop in blood pressure causes a response that increases SVR and cardiac output Remember the formula for BP…? BP = CO x SVR An increase in SVR and cardiac output together increase BP

16. Antihypertensive Drugs 90% of cases of hypertension are of unknown origin. idiopathic Idiopathic hypertension is also known as primary or essential hypertension. Hypertension is defined as having a systolic pressure of over 140 mm Hg and diastolic pressure over 90 mm Hg. Mild hypertension, between 140 – 159 mm Hg may initially be treated by changes in lifestyle More aggressive treatment is warranted as the problem gets worse.

17. Antihypertensive Drugs People who are hypertensive may initially experience few symptoms but over many years Prolonged high blood pressure can damage organs, especially the brain, kidneys and cardiovascular system and may result in haemorrhagic stroke, renal failure and myocardial infarction (heart attack). Atherosclerosis, a disease where fatty deposits accumulate and damage blood vessels is accelerated in people with high blood pressure, especially if they are also diabetic.

18. Antihypertensive Drugs All antihypertensive drugs act on the familiar formula… BP = SVR x CO (HR v SV) They act by 1.Reducing SVR.. or by... 2.Reducing cardiac output …by… 3.Reducing heart rate …or by… 4.Reducing stroke volume

19. Diuretics Diuretics stimulate the production of urine by the kidneys. Diuretics alter the osmotic balance in the kidney. This affects the kidney’s ability to reabsorb water from the filtrate passing through the nephron, so increasing the amount of urine produced. Increasing urine production lowers blood volume

20. Diuretics A reduction in blood volume reduces blood returning to the heart and so preload is reduced A reduction in preload reduces stroke volume CO = HR x SV Stroke volume and cardiac output decrease BP = CO x SVR Blood pressure decreases

21. Diuretics The glomerulus

22. Diuretics The nephron

23. Diuretics Diuretics reduce the rate at which water is reabsorbed. This results in more water being lost from the body and ultimately a fall in blood volume Loop diuretics Thiazide diuretics Potassium sparing diuretics

24. Angiotensin Converting Enzyme (ACE) inhibitors Examples – captopril, ramipril, perindopril etc. Used to treat hypertension and also heart failure ACE inhibitors interfere with the renin, angiotensin, aldosterone system that regulates long term BP. This system responds to a drop in blood pressure and works in conjunction with the baroreceptor reflex.

25. Renin, angiotensin, aldosterone system AngiotensinogenAngiotensin I Angiotensin II BP Renin Angiotensin Converting Enzyme

26. Renin, angiotensin, aldosterone system VasoconstrictionThirst Aldosterone Blood Pressure Sodium retention Angiotensin II ADH- vasopressin

27. Beta blockers

29. Beta-blockers Beta-blockers are beta-adrenoceptor antagonists. They bind to and block  1 receptors on the heart so reducing its responsiveness to sympathetic activity The action of  -blockers in reducing hypertension during rest is not well understood Probably involves the reduction of renin release Probably affects sympathetic activity in the central nervous system

30. Drugs acting on smooth muscle cells of the peripheral arterioles

31. Stimulation of muscle cells causes contraction and vasoconstriction

32. Drugs acting on smooth muscle cells of the peripheral arterioles

33. Angiotensin-II receptor blockers These drugs are used to treat essential hypertension and some are also used for heart failure. This group includes candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan and valsartan. Angiotensin-II is a potent vasoconstrictor that causes an increase in SVR Angiotensin-II receptor blockers bind to and block the AT1 receptor and therefore reduce the vasoconstrictive effect of angiotensin-II

34. Calcium-channel blockers (CCBs) Calcium-channel blockers (CCBs) exert their effects by different mechanisms. Drugs in this group licensed for the treatment of hypertension include, amlodipine, diltiazem, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nisoldipine and verapamil. Calcium channel blockers act on the heart’s conduction tissue to reduce heart rate, the myocardium to reduce stroke volume and the smooth muscles of the arterioles to reduce systemic vascular resistance.

35. Alpha-adrenoceptor blockers These drugs are generally used in combination with other hypertensives rather than on their own as mono- therapy. The group includes doxazosin, indoramin, prazosin and terazosin. Both circulating adrenaline and noradrenaline released as a neurotransmitter by the sympathetic nervous system binds to alpha-1 (  1) receptors on the arterioles with the same effect - vasoconstriction Blocking these receptors antagonistically means that neither adrenaline nor noradrenaline can bind and this results in relaxation of the smooth muscles of the arterioles and vasodilation.

36. End of Presentation