Lecture 5: Integrated Cardiovascular Regulation

The systemic __ is maintained at a relative constant 75-100 mmHg via intrinsic and extrinsic mechanisms.

mean arterial pressure (MAP)

The regulation of MAP is important for determining __ and __, particularly to the heart and brain.

capillary filtration pressures; regional blood flows

MAP - CVP =

CO x SVR

(delta P = Q x R)

Arterial pressure is a major factor determining __.

myocardial oxygen requirements

• inc in arterial pressure = inc afterload = inc in workload for heart to overcome = more oxygen required

Abnormally high __ pressures from hypertension lead to degenerative changes in __, resulting in serious and often fatal results.

transmural; arteries

transmural pressure = pressure difference from inside to outside of a vessel wall

__ is normally in the 2-8 mmHg range.

CVP/atrial pressure

Increase in __ (4) will ultimately increase venous pressure, venous return, EDV, and stroke volume.

• skeletal muscle pump

• inspiration movements

• activity of sympathetic nerves to veins

• blood volume

When there is a decrease in blood volume, reflexes like the __ will try to compensate for __ changes, while __ changes are regulated by the kidney and hormonal mechanisms.

baroreceptor; rapid; slower

Baroreceptors effectively __ short term changes in arterial pressure.

buffer

What is the short-term mechanism for changes in blood pressure?

baroreceptors

What is the short-term mechanism for changes in the chemical composition of blood?

chemoreceptors

The long-term regulation of blood pressure is mainly a function of the __, which regulate plasma volume by adjustments of: (2).

kidneys; water and salt excretion

this mechanism modulates preload to the heart via changes in blood volume

As a result of __ arterial pressure, an increased urinary loss of sodium and water in the kidneys will __ plasma volume and thus blood volume.

increased; decrease

Long-term regulation of __ is related to the renin-angiotensin system and the kidney.

MAP

Pressure within the afferent arteriole normally __ renin release.

inhibits

• afferent arteriole brings blood to kidney

Na flux through the distal tubule, sensed by macula densa cells, __ renin release.

inhibit

Discharge of sympathetic nerve fibers acting on granular cells __ renin release. Once released, renin acts on plasma angiotensinogen to form __ which is converted to __ by __.

stimulate; angiotensin I; angiotensin II; ACE

How does angiotensin II affect MAP?

Angiotensin II stimulates aldosterone secretion —> increases Na reabsorption —> increases fluid retention —> increases blood volume —> inc in blood volume & peripheral resistance = inc in arterial blood pressure

ACE inhibitor drugs __ MAP.

reduce

Pathological increases in renin can lead to __.

hypertension

What are the 4 effects of angiotensin II?

1. direct vasoconstriction

2. enhanced peripheral nor-adrenergic transmission

3. increased sympathetic discharge

4. release of catecholamines from adrenal medulla

ANF/ANP are secreted by atrial cells in the heart when they are __ by an increased __.

stretched; blood volume

ANF/ANP bind to NPR receptors to __ vascular smooth muscle (VSM) arterioles and increase capillary flow. In the kidney, this reduces Na+ reabsorption thus increases Na+ __ which ultimately __.

dilate; excretion; lowers blood pressure

Vasopressin can be released from the pituitary to __ water retention and thus __.

increase; blood volume

The baroreceptor reflex and hormones in the VSM both contribute to __ regulation.

water volume

ADH/vasopressin constricts VSM via the __ receptor. This increases water retention to maintain __.

V1; MAP

Angiotensin and ADH bind to __ receptors, whereas ANF/ANP binds to NPR, which is a __ receptor.

contraction activator; contraction inhibitor

Sympathetic release of __ and __ can ultimately alter vascular smooth muscle’s arteriolar radius (vasoconstrict/vasodilate).

epinephrine, NE

Alpha receptors are more sensitive to __, while beta receptors are more sensitive to __.

NE; epinephrine

At physiological levels, epinephrine __ VSM via the __ receptors.

vasodilates; beta2

At pharmacological levels, epinephrine __ VSM via the __ receptors, which overwhelms the vasodilation from __ sites.

vasoconstricts; alpha1; beta2

Application of epinephrine at pharmacological levels is a common dental practice to reduce __.

gum bleeding

The arterial __ reflex senses increased arterial pressure and starts firing to ultimately __ sympathetic outflow to heart, arterioles, and veins, and __ parasympathetic outflow to the heart.

baroreceptor; decrease; increase

Barorecptors are located in the: (2).

• carotid sinus

• aortic arch

An increase in __ (2) will increase the AP firing by baroreceptors.

MAP or elevated pulse pressure

Pressure is tightly regulated in a __ range.

narrow

At a certain high MAP value, baroreceptor AP frequency starts to plateau

When there is a hemorrhage, what mechanisms does the baroreceptor affect? (4)

1. chronotropic regulation

2. contractility

3. preload

4. afterload

When there is a mild volume loss, what 3 mechanisms occur to restore blood volume?

1. stimulation of efferent sympathetic fibers —> peripheral vasoconstriction

2. stimulation of renin secretion by kidney —> inc angiotensin II and aldosterone

3. antidiuretic hormone release

these prevent a decrease in arterial BP & restore lost blood volume by decreasing urinary water and sodium loss. heart rate isn’t affected

More severe/rapid levels of hemorrhage are associated with a decrease in __. This will trigger arterial baroreceptors, which increase: (2)

arterial blood pressure; heart rate & peripheral vascular resistance

As hemorrhage becomes more severe, __ sets in and reflex __ leads to peripheral vascular insufficiency.

hypotension; vasoconstriction

Receptors sensitive to chemical composition of blood are located in: (2)

• carotid body

• aortic body

arterial chemoreceptors = peripheral chemoreceptors, not central chemoreceptors

Arterial/peripheral chemoreceptors are more sensitive to arterial __ compared to __ & __.

P_O2; P_CO2; H+

Central chemoreceptors are most sensitive to __.

P_CO2

The main function of all chemoreceptors is to regulate __, but they also induce related __ changes, such as: (4).

ventilation; cardiovascular

• vascular resistance

• heart rate

• cardiac output

• blood pressure

Chemoreceptor stimulation causes widespread __, __ arterial pressure, and __ (bc of increased sympathetic efferent discharge).

vasoconstriction; increased; tachycardia

Blood pressure is normally maintained at __ levels via the rapid baroreceptor and chemoreceptor ANS reflexes.

constant

Baroreceptors are sensitive to vascular __, which is a function of __.

stretch; pressure

Baroreceptors are sensitive to both the: (2). With changes in these, the ANS can alter: (4)

• mean pressure

• rate of any change in pressure

• heart rate, contractility, preload, vascular resistance

Local control falls into what 2 general categories?

1. active hyperemia

2. flow autoregulation

Arterioles that control the flow into an organ usually lie __ that organ. Thus, interstitial concentrations of __ or __ concentrations in that organ can influence blood flow by vasoconstricting or vasodilating local vessels.

within; metabolites; O2/CO2/H+/K+/NO

Metabolites & O2/CO2/H+/K+ can enter the circulation and elicit more global ANS mediated responses via the __.

metaboreflex

Endothelial cells modulate __ & __ for vasodilation, and __ for vasoconstriction.

NO; prostacyclin; endothelin

Prostaglandins, histamines, bradykinin, adenosine, and other substances released during injury can elicit __.

vasodilation

some of these work directly or in conjunction with endothelial cells

Explain what this graph is showing.

In organs with highly variable metabolic rates, the flow patterns closely follow the tissue’s metabolic rate.

in skeletal muscle, flow increases within seconds upon onset of exercise and returns to ocntrol at end of exercise = active hyperemia / high flow

Explain what this graph is showing.

temporary restriction to flow —> higher than normal BP occurs transiently following removal of restriction = reactive hyperemia (= myogenic response to reduced transmural pressure & accumulation of metabolites/CO2)

What is autoregulation?

organs keep blood flow constant despite variations in arterial pressure

occurs except when displaying active or reactive hyperemia

What does this graph show about autoregulation?

in presence of sustained increase in pressure, organ blood flow initially goes up, then drops back down to close to original level (autoregulation).

Flow rate changes from pressure changes will __ or __ metabolites —> fostering a new steady state.

wash out; retain

Direct vessel stretch or reduction from pressure changes will induce __ modulation of smooth muscle contraction.

myogenic

What factors modulate the blood flow via arterial smooth muscle? (3)

1. hormonal: vasoconstrictors (NE, angiotensin II, ADH, epinephrine @ high doses); vasodilators (ANF, histamine, epinephrine @ physiological levels)

2. neural: baroreceptors, chemoreceptors

3. local: metabolites, O2/CO2, myogenic response, osmolarity, local NO

Among the many hormones and factors released, the __ and __ impact the CV system the most, and sometimes can be detrimental.

catecholamines; cortisol

Cortisol affects vascular smooth muscle by enhancing the __ of vascular smooth muscle to __ stimuli (NE).

reactivity; vasoconstricting

Stress activates __ stimulation of the adrenal medulla to secrete catecholamines (primarily __).

sympathetic; epinephrine

Epinephrine [increases/decreases] skeletal muscle fatigue, [increases/decreases] cardiac contractility (thus [increasing/decreasing] cardiac output), and shunts __ from visceral organs to skeletal muscle by constricting visceral blood and vasodilating skeletal muscle blood vessels.

decreases; increases; increasing; blood

decreases skeletal muscle fatigue —> allows muscles to remain active for longer periods (fight or flight)

What are the adaptive advantages of chronic stress?

none: has deleterious effects on physiological processes

can eventually lead to atherosclerosis, arrhythmias, HTN, heart failure

What is a useful function of stress (not chronic)?

increases total peripheral vascular resistance and thus decreases probability of developing hypotension during moderate stress