Resistance arteries have been recognized for some time as key factors in the regulation of vascular flow resistance, where they determine the regional and local distribution of blood and arterial pressure. Chapters provide an overview of the physiological, biochemical, and electrophysiological characteristics of these vessels, as well as a critical evaluation of the methodologies for studying small arteries and an examination of the membrane and neural mechanisms involved in the control of vascular tone.

Much of our knowledge of the cerebral circulation has been derived from studies of species other than human. There is increas­ ing recognition of species differences and concern that studies in animals may be misleading if unquestioningly applied to the human. A dramatic example of this occurred in the early his­ tory of the study of the circulation of the brain. Galen of Pergamo (131-201 AD) described a rete mirabile or "marvelous network" of blood vessels at the base of the human skull that he must have derived from observations of certain animals. This vascular structure was supplied by the carotid arteries which, after penetrating the cranium,"are divided into a large number of very small and thin branches in the region between the cranium and the dura matter. Then . . . intersecting one another they give the impression of having forgotten their way in the brain. But this is not the case. In fact, these numerous arteries rejoin and unite like the roots of a tree trunk. . . . " The authority of Galen's writings dominated scientific thought for about 1500 years. His description of a rete was unques­ tioned by Leonardo de Vinci, who included it in his anatomical sketches. William Harvey's remarkable observations led to his definitive account of the circulation of blood.

The Resistance Arteries is focused on the general issue of the regulatory pathways in resistance arteries and comprises a selection of timely overviews and up-to-date research studies presented at the 4th International Symposium on Resistance Arteries. These small vessels act as major controllers of blood pressure, blood flow, and its distribution, and are involved in a variety of pathological conditions. Vascular diameter is influenced by a host of factors, some extrinsic to the smooth musc1e cells and some intrinsic. One will find contributions in nearly all of the five themes by which the book is organized; these address intra-and extracellular interactions, and membrane receptor pathways using vascular beds as diverse as the brain, he art, lung, kidney, and skin. Basic physiological studies are inc1uded; these examine: growth fac- tors, vasoactive endothelium-derived nitric oxide, the impacts of flow and stretch, myogenic mechanisms, calcium regulation by protein kinase C, and signal transduction pathways of the vascular smooth musc1e cell membrane receptors.Not only are tissues from appropriate animal models exploited in most of these reports, but many reflect the current increase in the use of human tissue to elucidate vascular alterations of function and morphology in hypertension, atherosclerosis, and ischemia. Noteworthy among the many techniques used are: membrane permeabilization with toxins, fura-2 for calcium determination, single cell electrophysiology, and the application of confocal microscopy to isolated, living vessels.

Much of our knowledge of the cerebral circulation has been derived from studies of species other than human. There is increas­ ing recognition of species differences and concern that studies in animals may be misleading if unquestioningly applied to the human. A dramatic example of this occurred in the early his­ tory of the study of the circulation of the brain. Galen of Pergamo (131-201 AD) described a rete mirabile or "marvelous network" of blood vessels at the base of the human skull that he must have derived from observations of certain animals. This vascular structure was supplied by the carotid arteries which, after penetrating the cranium,"are divided into a large number of very small and thin branches in the region between the cranium and the dura matter. Then . . . intersecting one another they give the impression of having forgotten their way in the brain. But this is not the case. In fact, these numerous arteries rejoin and unite like the roots of a tree trunk. . . . " The authority of Galen''s writings dominated scientific thought for about 1500 years. His description of a rete was unques­ tioned by Leonardo de Vinci, who included it in his anatomical sketches. William Harvey''s remarkable observations led to his definitive account of the circulation of blood.

Resistance arteries have been recognized for some time as key factors in the regulation of vascular flow resistance, where they determine the regional and local distribution of blood and arterial pressure. Chapters provide an overview of the physiological, biochemical, and electrophysiological characteristics of these vessels, as well as a critical evaluation of the methodologies for studying small arteries and an examination of the membrane and neural mechanisms involved in the control of vascular tone.

Much of our knowledge of the cerebral circulation has been derived from studies of species other than human. There is increas­ ing recognition of species differences and concern that studies in animals may be misleading if unquestioningly applied to the human. A dramatic example of this occurred in the early his­ tory of the study of the circulation of the brain. Galen of Pergamo (131-201 AD) described a rete mirabile or "marvelous network" of blood vessels at the base of the human skull that he must have derived from observations of certain animals. This vascular structure was supplied by the carotid arteries which, after penetrating the cranium,"are divided into a large number of very small and thin branches in the region between the cranium and the dura matter. Then . . . intersecting one another they give the impression of having forgotten their way in the brain. But this is not the case. In fact, these numerous arteries rejoin and unite like the roots of a tree trunk. . . . " The authority of Galen's writings dominated scientific thought for about 1500 years. His description of a rete was unques­ tioned by Leonardo de Vinci, who included it in his anatomical sketches. William Harvey's remarkable observations led to his definitive account of the circulation of blood.

Resistance arteries have been recognized for some time as key factors in the regulation of vascular flow resistance, where they determine the regional and local distribution of blood and arterial pressure. Chapters provide an overview of the physiological, biochemical, and electrophysiological characteristics of these vessels, as well as a critical evaluation of the methodologies for studying small arteries and an examination of the membrane and neural mechanisms involved in the control of vascular tone.

Exactly sixty years ago Schretzenmayer provided the first experimental proof that changes in blood ftow can affect the diameter oflarge arteries. Since then, support has been growing for the idea that intraluminal blood ftow plays an important role in regulating not only the tone of blood vessels, but also their caliber and structure. Investigations of the&e phenomena have been given a strong impetus by the discovery that the endothelium can modulate the tone of underlying vascular smooth muscle via the release of a number of vasoactive substances. Investigators often diverge in their opinions regarding the nature of the vascular wall response to blood ftow and the mechanisms involved. This book is the first summary of our state of knowledge and the nature of the research carried out on ftow-related changes. Early chapters review involvement of shear-stress-dependent events in the circulation as a whole. They cover the biophysical principles of ftuid transport, the cellular signal transduction path­ ways, and the molecular biology and biochemistry of ftow-induced changes in endothelial cells. Later chapters provide an in-depth summary of the regula­ tion of vascular muscle tone by ftow. They include historical perspectives, evi­ dence that ftow-induced vasodilation is primarily endothelium-dependent and that it can induce constriction, and details on ftow-dependent regulation in regional vascular beds. Several chapters emphasize the endothelial activation by shear stress and its importance in the control offtow in the microcirculation.

Resistance arteries have been recognized for some time as key factors in the regulation of vascular flow resistance, where they determine the regional and local distribution of blood and arterial pressure. Chapters provide an overview of the physiological, biochemical, and electrophysiological characteristics of these vessels, as well as a critical evaluation of the methodologies for studying small arteries and an examination of the membrane and neural mechanisms involved in the control of vascular tone.

Much of our knowledge of the cerebral circulation has been derived from studies of species other than human. There is increas­ ing recognition of species differences and concern that studies in animals may be misleading if unquestioningly applied to the human. A dramatic example of this occurred in the early his­ tory of the study of the circulation of the brain. Galen of Pergamo (131-201 AD) described a rete mirabile or "marvelous network" of blood vessels at the base of the human skull that he must have derived from observations of certain animals. This vascular structure was supplied by the carotid arteries which, after penetrating the cranium,"are divided into a large number of very small and thin branches in the region between the cranium and the dura matter. Then . . . intersecting one another they give the impression of having forgotten their way in the brain. But this is not the case. In fact, these numerous arteries rejoin and unite like the roots of a tree trunk. . . . " The authority of Galen's writings dominated scientific thought for about 1500 years. His description of a rete was unques­ tioned by Leonardo de Vinci, who included it in his anatomical sketches. William Harvey's remarkable observations led to his definitive account of the circulation of blood.

The Resistance Arteries is focused on the general issue of the regulatory pathways in resistance arteries and comprises a selection of timely overviews and up-to-date research studies presented at the 4th International Symposium on Resistance Arteries. These small vessels act as major controllers of blood pressure, blood flow, and its distribution, and are involved in a variety of pathological conditions. Vascular diameter is influenced by a host of factors, some extrinsic to the smooth musc1e cells and some intrinsic. One will find contributions in nearly all of the five themes by which the book is organized; these address intra-and extracellular interactions, and membrane receptor pathways using vascular beds as diverse as the brain, he art, lung, kidney, and skin. Basic physiological studies are inc1uded; these examine: growth fac- tors, vasoactive endothelium-derived nitric oxide, the impacts of flow and stretch, myogenic mechanisms, calcium regulation by protein kinase C, and signal transduction pathways of the vascular smooth musc1e cell membrane receptors.Not only are tissues from appropriate animal models exploited in most of these reports, but many reflect the current increase in the use of human tissue to elucidate vascular alterations of function and morphology in hypertension, atherosclerosis, and ischemia. Noteworthy among the many techniques used are: membrane permeabilization with toxins, fura-2 for calcium determination, single cell electrophysiology, and the application of confocal microscopy to isolated, living vessels.

Much of our knowledge of the cerebral circulation has been derived from studies of species other than human. There is increas­ ing recognition of species differences and concern that studies in animals may be misleading if unquestioningly applied to the human. A dramatic example of this occurred in the early his­ tory of the study of the circulation of the brain. Galen of Pergamo (131-201 AD) described a rete mirabile or "marvelous network" of blood vessels at the base of the human skull that he must have derived from observations of certain animals. This vascular structure was supplied by the carotid arteries which, after penetrating the cranium,"are divided into a large number of very small and thin branches in the region between the cranium and the dura matter. Then . . . intersecting one another they give the impression of having forgotten their way in the brain. But this is not the case. In fact, these numerous arteries rejoin and unite like the roots of a tree trunk. . . . " The authority of Galen''s writings dominated scientific thought for about 1500 years. His description of a rete was unques­ tioned by Leonardo de Vinci, who included it in his anatomical sketches. William Harvey''s remarkable observations led to his definitive account of the circulation of blood.

Resistance arteries have been recognized for some time as key factors in the regulation of vascular flow resistance, where they determine the regional and local distribution of blood and arterial pressure. Chapters provide an overview of the physiological, biochemical, and electrophysiological characteristics of these vessels, as well as a critical evaluation of the methodologies for studying small arteries and an examination of the membrane and neural mechanisms involved in the control of vascular tone.

Much of our knowledge of the cerebral circulation has been derived from studies of species other than human. There is increas­ ing recognition of species differences and concern that studies in animals may be misleading if unquestioningly applied to the human. A dramatic example of this occurred in the early his­ tory of the study of the circulation of the brain. Galen of Pergamo (131-201 AD) described a rete mirabile or "marvelous network" of blood vessels at the base of the human skull that he must have derived from observations of certain animals. This vascular structure was supplied by the carotid arteries which, after penetrating the cranium,"are divided into a large number of very small and thin branches in the region between the cranium and the dura matter. Then . . . intersecting one another they give the impression of having forgotten their way in the brain. But this is not the case. In fact, these numerous arteries rejoin and unite like the roots of a tree trunk. . . . " The authority of Galen's writings dominated scientific thought for about 1500 years. His description of a rete was unques­ tioned by Leonardo de Vinci, who included it in his anatomical sketches. William Harvey's remarkable observations led to his definitive account of the circulation of blood.

Resistance arteries have been recognized for some time as key factors in the regulation of vascular flow resistance, where they determine the regional and local distribution of blood and arterial pressure. Chapters provide an overview of the physiological, biochemical, and electrophysiological characteristics of these vessels, as well as a critical evaluation of the methodologies for studying small arteries and an examination of the membrane and neural mechanisms involved in the control of vascular tone.

Exactly sixty years ago Schretzenmayer provided the first experimental proof that changes in blood ftow can affect the diameter oflarge arteries. Since then, support has been growing for the idea that intraluminal blood ftow plays an important role in regulating not only the tone of blood vessels, but also their caliber and structure. Investigations of the&e phenomena have been given a strong impetus by the discovery that the endothelium can modulate the tone of underlying vascular smooth muscle via the release of a number of vasoactive substances. Investigators often diverge in their opinions regarding the nature of the vascular wall response to blood ftow and the mechanisms involved. This book is the first summary of our state of knowledge and the nature of the research carried out on ftow-related changes. Early chapters review involvement of shear-stress-dependent events in the circulation as a whole. They cover the biophysical principles of ftuid transport, the cellular signal transduction path­ ways, and the molecular biology and biochemistry of ftow-induced changes in endothelial cells. Later chapters provide an in-depth summary of the regula­ tion of vascular muscle tone by ftow. They include historical perspectives, evi­ dence that ftow-induced vasodilation is primarily endothelium-dependent and that it can induce constriction, and details on ftow-dependent regulation in regional vascular beds. Several chapters emphasize the endothelial activation by shear stress and its importance in the control offtow in the microcirculation.