G4iv: Explain the humoral regulation of blood volume & flow

Definition

Humoral Substance = substance circulating in blood

→ Affect cardiac & vascular function

→ Mainly:

    • CATECHOLAMINES
    • RAAS
    • ANP
    • VASOPRESSIN
    • ENDOTHELIN
    • Also: thyroxine, O, Insulin, GH

Catecholamines

  • Adrenal Medulla secretes 80% adrenaline, 20% NA
  • nerves of vessels release catecholamines (mainly NA)
  • ADRENALINE: α1, α2, β1, β2 agonism
    • β > α affinity
    • Low [Adr]: β1 effects predominate → +HR, +ino, +chrono

                    β 2 arteriolar VD

    • High [Adr]: α & β agonism
      • α1 → smooth m. VC → ↑CO + ↑SVR = ↑BP but β2 effect limits this (unless pt is β blocked)

Noradrenaline: α1, α2, β1, β2

  • Affinity α1 & β1
  • ↑MAP (↑VC)
  • ↑Pulse pressure (↑SV)
  • ↑HR (β1 agonism of SA node) = initially
  • Then → reflex ↓HR (BaroR reflex)

RAAS

  • Important for:
    • Regulation blood volume
    • Cardiac & Vascular function
    • BP

Renin

  • 3 stimuli for RENIN release
    1. stimulation by β1 receptors
    2. Renal A hypoT
    3. ↓Na+ delivery to distal tubules
  • Released by Juxtaglom. Cells
  • An enzyme
Angiotensinogen

AII

  1. Powerful VC of Resistance Vessels → ↑SVR → ↑BP
  2. ↑SYMP ACTIVITY
    • ↑NA release from symp n.
    • Inhibits NA reuptake
    • Binds AT, Receptor of RVLM → ↑symp. outflow
  3. Acts on ADRENAL CORTEX → release ALDOSTERONE

→ ↑NaCl/H2O reabs → volume expansion

  1. ↑VASOPRESSIN release from PPG
  2. Stimulates thirst centre → ↑ blood volume
  3. Stimulates cardiac & ventricular hypertrophy

ANP

  • Peptide synth, stored & secreted by atrial myocytes
  • Released: atrial distension, AII stimulation, endothelin, symp. β adrenaline stimulation
  • Long term regulation: blood vol, NaCl/H2O balance, arterial P
  • Opposite effect of AII:
    • ↓Aldosterone release
    • ↓RENIN → ↓AII
    • ↑GFR → Natiuresis & diuresis

Vasopressin

  • Nonapeptide hormone
  • Released by PPU
  • 2 sites of action:
    1. V1 → vessels → VC
    2. V2 → collecting duct → ↑H2O reabsorption = ↑BP

Endothelin

  • Potent VC produced by endothelial cells
  • Stimulated by AII, ADH, Thrombin, cytokines, ROS, shear forces

Inhibited by NO, ANP, prostacyclin

Thyroid Hormone

  • ↓SVR (smooth m. relaxation)
  • ↑Sensitivity to catechol.
  • ∴↑HR & ↑CO

Insulin: High dose = +ve inotropy

GH: + inotropy

OESTROGEN: ↓SVR, ↑plasma volume