Macro- and

microcirculation in

clinical hypertension

경북대학교병원

순환기내과

양 동 헌

The Vein Man. Vesalius (1554)

Macrocirculation

Microcirculation

Definition of microcirculation

Morphology

Functions of microcirculation

Nutrient & oxygen supply

in response to variations in demand

Avoiding large fluctuations in

hydrostatic pressure

Drop in hydrostatic pressure

Overall peripheral vascular resistance

Factors contributing to arterial stiffness

Endothelialdysfunction

↑Arterialstiffness

AgingElastinfacture

Aging↑Collagendeposition

LV dysfunctionLV hypertrophy

↑Pulse pressureHypertension

Ischemia↑ metabolic demand

Hyperglycemia

DyslipidemiaHyperinsulinemia

HypertensionOxidativestressObesity

SmokingSedentary

life

Time course of change in arterial stiffness

SmallArteryResponse

ConduitArteryResponse

SmallArteryStructure

ConduitArteryStructure

AortaStructure

Small arteryelasticity (C2)

FMD AIxC2BiopsyRetinaMicro-albuminuriaBP ↑

IMTLarge arteryelasticity (C1)Exercise BPPres:Vol

PWVAIxPPC1

Cohn JN et al. Hypertension 2005;46:217

EarlyFunction

LateStructure

Methods of evaluation

Macrocirculation PWV AI Elastic modulus Arterial distensibility Compliance Stiffness index PP IMT

Microcirculation In vitro

Isolated small artery

Direct visualization Intravital capillaroscopy Orthogonal polarization

spectal imaging microscopy

Regional measurement Venous occlusion

plethysmography

Surface measurement Laser doppler flux

measurement PET, MRI Contrast echo

Factors affecting to PWV

Increase ofArterial stiffness

Hyperglycemia

DyslipidemiaHyperinsulinemia

HypertensionOxidativestressObesity

SmokingSedentary

life

PWV and CVD

↑ PWV

HypertensionCVD risk

Mortality in HT, DM, CRF Plaque

StrokeDementia

Systemic microvessels in cardiac syndrome X

Intravital

videocapillaroscopy

Metabolic syndrome

Hypertension

Obesity Insulin

Resistance

Microcirculatory

Dysfunction

Microvascular dysfunction in hypertension

Abnormal regulation of vasomotor tone Vasoconstriction ↑ / vasodilator response ↓

Alteration (remodeling) in the structure of individual precapillary resistance vessels Increase in their wall-to-lumen ratio

Vascular rarefaction Reduction in the number of arterioles or

capillaries

Microvascular dysfunction in hypertension

Impaired skin capillary recruitment Structural capillary number ↓

Functional nonperfusion

62% : structural defect

38% : functional defect

Hypertension. 2001;38:238–242

Microvascular dysfunction: Result vs Cause ???

Intermittent HTN

Genetic predisposition

Metabolic components

Microvascular dysfunction

Capillary rarefaction

Vascular remodeling

Microvascular dysfunction: Result vs Cause ???

Intermittent HTN

Genetic predisposition

Metabolic components

Microvascular dysfunction

Capillary rarefaction

Vascular remodeling

- Microvascular rarefaction in subjects with mild intermittent HTN & in

normotensives with a genetic predisposition to HTN

- Capillary rarefaction in muscle to predict the increase in MAP

-Smaller retinal arteriolar diameter to predict the occurrence & development

of HTN in a prospective population study

- Subtle renal microvascular disease & reduced number of nephrons (Borst-

Guyton concept)

Microvascular dysfunction in obesity

J Clin Endocrinol Metab. 2006;91:5100–5106

Microvascular dysfunction in obesity

Impaired insulin-dependent capillary recruitment

Normal physiology of insulin

Increase of total blood flow & volume in skeletal muscle Higher concentration

“Functional capillary recruitment” Redistribution of blood flow in nutritive compared with

nonnutritive vessels, independent of total muscle flow

Associated with changes in skeletal muscle glucose uptake independently of changes in total blood flow

Lower concentration

Augmentation of the access of glucose to insulin-sensitive tissues (muslce)

Microvascular dysfunction as a cause of insulin resistance

Impaired ability of insulin to dilate skeletal muscle vasculature

Impairment of the insulin-dependent capillary recruitment

Impairment of the access of macromolecules (glucose) to insulin-sensitive tissues Subnormal capillary permeability-surface

area product (PS) for glucose & insulin

Laser Doppler flow measurements

Microvascular dysfunction as a cause of insulin resistance

Important roles of the microcirculation in

regulating nutrient & hormone access to

musle

Any impairment in capillary recruitment

Impairment in glucose uptake by muslce

Possible mechanisms

Vasocrine signalling

Obese Zucker rats

Microvascular function & aortic stiffness

Microvascular function FVR : forearm vascular resistance

Aortic stiffness : CF-PWV

Microvascular dysfunction: Result vs Cause ???

Hypertension

Aortic stiffness ↑

Forward wave amplitude ↑

Microvascular dysfunction

Capillary rarefaction

Vascular remodeling

Postulated causative role of microvascular dysfunction