Lecture 29

Question 1

Systemic vascular resistance

Answer 1

AKA total peripheral resistance. One of the main determinants of arterial BP. Smaller muscular arteries and arterioles are the main resistance vessels while veins are capacity vessels that contain a large fraction of the total blood volume therefore arteries/arterioles regulate afterload while veins and pulmonary vessels regulate preload. Viscoelastic properties of arteries determine arterial compliance.

Question 2

Systems involved in BP regulation

Answer 2

• Vascular endothelium
• Sympatho-adrenomedullary systems
• Renin-angiotensin-aldosterone system

Question 3

Vascular endothelium

Answer 3

Prostaglandin 12 (PG12) is synthesised in endothelial cells and acts on IP receptors on SM to dilate it. Prostaglandin intermediates are endothelial derived contracting factors that act on thromboxane T prostanoid receptors. NO released tonically in resistance vessels giving rise to vasodilator tone and contributing to BP control. Angiotensin II formed by ACE which sits on endothelial cells and acts on AT1 receptors on SM causing vasoconstriction.

Question 4

Sympatho-adrenomedullary system

Answer 4

AKA sympathetic NS. Composed of preganglionic nerves (spinal nerves exiting thoracolumbar region of spinal cord) to synapse with ganglia. Post-ganglionic nerves synapse with viscera and vasculature. For BP, acts on heart, SM and kidneys. Preganglionic nerves exit spinal cord and synapse with adrenal medulla to release adrenaline. In circulation, adrenaline acts on adrenoceptors found on many organs apart on SAM.

Question 5

Adrenoceptors

Answer 5

All GPCR (metabotropic). Alpha and beta. At low [adrenaline], B1 and B2 receptors activated while increasing [adrenaline], B1, B2 and alpha receptors. Noradrenaline has lower affinity for B2 adrenoreceptors, acting on mostly alpha1 and beta1. Adrenaline released from adrenal medulla for circulation while noradrenaline from post-ganglionic nerves.

Question 6

Action of sympatho-adrenomedullary system

Answer 6

In the heart, B1 receptor activation increases HR (positive chronotropic effect) and increases force of contraction (positive inotropic effect). As CO relies on HR and SV, increase in HR due to B1 activation = increase CO. As BP is dependent on CO and SVR, increase in CO = increase BP, alpha1 activation causes vasoconstriction. Mesenteric vasculature makes a significant contribution to overall vascular resistance. Activation of B1 receptors juxtaglomerular cells causes renin release = vasoconstriction = increase BP.

Question 7

Renin-angiotensin-aldosterone system

Answer 7

Works synergistically with sympathetic NS to control BP. Noradrenaline triggers aldosterone secretion to control Na+ excretion, fluid volume and vascular tone. Renin is secreted by juxtaglomerular apparatus of kidney in response to decrease renal perfusion, decrease [Na+] in distal tubule. Renal sympathetic nerve activity, B agonists and PGI 2 stimulate renin secretion while angiotensin II causes feedback inhibition. Renin acts on angiotensinogen to form angiotensin I. Activated by ACE on surface of endothelial cells. Ang. II stimulates sympathetic activity and vasopressin increases BP. AT1 receptors causes vasoconstriction, increase noradrenaline release, increase Na+ reabsorption in proximal tubules, increases aldosterone secretion by adrenal cortex and proinflammatory impacts. Na+ retention increases BV, increases BP.

Question 8

lifestyle modifications

Answer 8

• Exercise
• weight loss (if overweight)
  -decrease saturated fat
• decrease Na+
• Increase fruit and fibre
• limit alcohol
• stress reduction technique
• 7-9hr sleep