Neuroendocrine function and Hypothalamic control

1. Neuroendocrine function and Hypothalamic control

2. Neuronal regulation (e.g., of the cardiovascular system);what is the point? • CV system regulates quite well with no neuronal input. Heart beat regulated by intrinsic pacemakers and arteriolar constriction regulated by local agents and circulating hormones. • At rest that is fine, but when the organism is challenged, then there is a need to alter overall CV output and local circulation.

4. Parallel pathways regulate arterial pressure, but their time constants are very different.

5. Blood volume • Intake – output. • Regulated by Aldosterone, Angiotensin, Atrial Natriuretic Peptide, Vasopressin, etc. • Kidney main organ regulating volume homeostasis.

6. It’s the flow that is important Regional blood flow is important and acute changes in it are largely regulated by the nervous system.

7. What are the ultimate neuronal controls of blood flow • Sympathetic nervous system (NE+) • Parasympathetic nervous system (Ach+) • Circulating hormones • Locally released hormones • Local neuronal and glial regulation in the brain

8. Feedback control of nervous system regulation of CV system • Baroreflexes • Chemoreceptors • O2/CO2 receptors • Pain • exercise • Stretch • Heat • Nutrition

9. Baroreflexes • High pressure receptors in the aorta and carotid artery • Low pressure (cardiopulmonary receptors) atria

10. Both the IX and X nerves carry baroreceptor information to the brain. Other baroreceptors located throughout the body organs, but their influence is less global.

11. Variability of AP control without baroreceptor feedback.

12. Chemoreceptors • Especially sensitive to O2 and CO2

14. CNS regulated neurohormones in CV control

15. SNS activates renin release in the kidney • Renin in the circulation converts anagiotensinogen to A I and ACE converts AI to vasoactive AII. • Also regulated by plasma ions (esp. NaCl) • Local AII system in brain and kidney and heart.

16. Renin-Angoiotensin/nervous system interplaypromotes vasoconstriction via • Directly acting through AT1 receptors on arterioles • Increasing presynaptic release of NE from sympathetic nerves • Blunting baroreflex restraint • Activating circumventricular organs, esp. SFO and AP to increase SNS activity and drinking and regulates vasopressin

17. Vasopressin(AntiDiuretic Hormone; ADH) • Released into the circulation by neurons in the hypothalamus • Circulating AVP elicits vasoconstriction via V1 receptors and induces antidiuresis via v2 receptors in the kidney • Also alters baroreflex and tonic control of SNS activity by direct release from neurons and circulating AVP diffusing to neurons

18. CNS controls Norepinephrine (NE) & Epinephrine (Epi) release, but these catecholamines have different actions • Beta-adrenergic receptors have much higher affinity for Epi << NE, while alpha-AR have the opposite affinity. • Beta-AR (vasodilatory) numerous on heart and arterioles in heart and skeletal muscle • Alpha-AR much more prominent on peripheral arterioles and vasoconstrict. • Stimulation of adrenal medulla increases heart and skeletal muscle related vasodilation and HR.

19. Unlike an injection of NE which raises BP and HR via alpha1-AR equally, epinephrine injections act primarily on beta-AR increasing HR/contractility and thereby increasing CO. BF is increased to the skeletal muscle heart and brain but decreased to the kidney and skin. TPR is reduced as reflected in decrease in diastolic pressure. Increase in CO reflected in increased systolic arterial pressure.

20. VII. Autonomic Nervous System

21. Integrated Neurendocrine regulation of the CV system

22. Brain areas involved in neuroendocrine and autonomic regulation

23. Rostral Ventral Lateral Medulla (RVLM) • RVLM generates sympathetic tone. • Appears that the RVLM vasomotor neurons are final integrators of a large amount of information relative to CV control.

24. Sensory regulation of RVLM via nucleus of the solitary tract (NTS) • Both high and low pressure baroreceptor feedback to the brain synapses in the NTS • Gustatory and other inputs also reach NTS in discrete regions • The NTS has widespread projections to forebrain and medulla

25. NTS AP

26. Brainstem BP control pathway ANGIOTENSIN

27. Higher control

28. I. Hypothalamus (Head autonomic ganglion) Hypothalamus Optic chiasm Fig. 1.3

29. Hypothalamus as Homeostatic Regulator Parent, 17.1

30. Vegetative function of hypothalamus;regulation of eating, drinking and digestion Parent, Fig. 17.1

31. Areas that receive information about warmthPreoptic areaAnterior hypothalamic area Parent, 17.1

32. Sympathoinhibitory nuclei • Warm receptors • Activation leads to inhibition of SNS • Sweating • Vasodilaiton • Pyrogens bind here and allow fever to continue by changing setpoint • Renal excretion • Drinking regulation (defending against dehydration and overheating)

33. Circadian rhythm • Suprachiasmatic nucleus • Sets rhythm of AP/HR • Daily blood pressure rhythm can be over 30 mmHg and reduction in nighttime dip is sign if potential organ damage • Normal rhythm is slightly over 24 hours, but this is entrained by light to the eye • Interesting regulation via sympathetic innervation of pineal gland, thereby releasing melatonin

35. Circadian rhythm Circadian output of SCN via sympathetic nervous system Regulates melatonin release from the pineal Which modulates sleep and sex

36. B. Activating nuclei to respond to cold or stress Shut down eating/peristalsis Shiver Renal inhibition Vasoconstrict non-required vascular beds Increase blood flow to skeletal muscle Parent, 17.1

37. Sympathoexcitatory nucleiPHA • Direct projection to the spinal cord • May provide direct hypothalamic modulation of CV system • Cold sensors (defense of body heat) • Vasodilation • Shivering

38. Sympathoexcitatory nucleiVMH • Important in the defense/escape reaction and also in eating and sexual activity

39. Sympathoexcitatory nucleiLHA • Homeostatic regulator • Leptin, glucose and insulin receptors

40. Monitoring inner world Circumventricular organs • Organum vasculosum of the lamina terminalis (OVLT) • sodium and osmotic sensitivity • Subfornical organ (SFO) • Angiotensin II • Area postrema (AP) • Toxin monitoring

41. D. Endocrine control Parent, Fig. 17.20

42. Circulating Neuroendocrine Elements Parent, 17.1

43. Paraventricular (PVN) and supraoptic nucleus Vasopressin Oxytocin Hormone regulators Circulating hormones Fig. 11.16

44. E. Anterior lobe controled by arcuate nuclei, e.g., sexual function, etc. Parent, 17.20, 17.1

45. Interactions of neuropeptides and other transmitters in autonomic control

46. Natriuretic peptide family • ANP causes inhibition of NE release in CNS and PNS (i.e. it acts opposite of AII). • In PNS cause reduction in AP and increased diuresis/natriuresis • In hypothalamus it causes the opposite effects. • Regional distribution of ANP and receptors underlie this effect. ANP inhibition of NE throughout the hypothalamus causes differential effects.

47. Sex steroids and Vasopressin/Oxytocin • SON/PVN • Increases dendritic activation (electrical and chemical) by juxtaposing the dendrites. • Regulation of fluid volume, memory, sex, etc.

48. Beer Stories • Drink beer; lots of beer fast • About 30 minutes later need to urinate badly • Why?? • What happens if you keep drinking?

49. Beer Potomania • Potomania: An intense and persistent desire to drink alcohol to excess. • Dilutional hyponatraemia • Pass out/death

50. Why? • Decrease ADH (vasopressin) as much as possible in first hour • Continue ingestion of fluid low in solutes and lack of protein intake • Decrease in plasma Na and osmolality • Kidneys can only excrete limited load