Background Experimental evidence suggests that flow-dependent dilatation of conduit arteries is mediated by nitric oxide (NO) and/or prostacyclin. The present study was designed to assess whether NO or prostacyclin also contributes to flow-dependent dilatation of conduit arteries in humans. Methods and Results Radial artery internal diameter (ID) was measured continuously in 16 healthy volunteers (age, 24±1 years) with a transcutaneous A-mode echo-tracking system coupled to a Doppler device for the measurement of radial blood flow. In 8 subjects, a catheter was inserted into the brachial artery for measurement of arterial pressure and infusion of the NO synthase inhibitor NG-monomethyl-l-arginine (L-NMMA; 8 μmol/min for 7 minutes; infusion rate, 0.8 mL/min). Flow-dependent dilatation was evaluated before and after L-NMMA or aspirin as the response of the radial artery to an acute increase in flow (reactive hyperemia after a 3-minute cuff wrist occlusion). Under control conditions, release of the occlusion...

Nitric Oxide Is Responsible for Flow-Dependent Dilatation of Human Peripheral Conduit Arteries In Vivo

Much has been published in the past 20 years on the use of measurements of arterial stiffness in animal and human research studies. This summary statement was commissioned by the American Heart Association to address issues concerning the nomenclature, methodologies, utility, limitations, and gaps in knowledge in this rapidly evolving field. The following represents an executive version of the larger online-only Data Supplement and is intended to give the reader a sense of why arterial stiffness is important, how it is measured, the situations in which it has been useful, its limitations, and questions that remain to be addressed in this field. Throughout the document, pulse-wave velocity (PWV; measured in meters per second) and variations such as carotid-femoral PWV (cfPWV; measured in meters per second) are used. PWV without modification is used in the general sense of arterial stiffness. The addition of lowercase modifiers such as “cf” is used when speaking of specific segments of the arterial circulation.

The ability to measure arterial stiffness has been present for many years, but the measurement was invasive in the early times. The improvement in technologies to enable repeated, minimal-risk, reproducible measures of this aspect of circulatory physiology led to its incorporation into longitudinal cohort studies spanning a variety of clinical populations, including those at extreme cardiovascular risk (patients on dialysis), those with comorbidities such as diabetes mellitus (DM) and hypertension, healthy elders, and general populations.

In the ≈3 decades of clinical use of PWV measures in humans, we have learned much about the importance of this parameter. PWV has proven to have independent predictive utility when evaluated in conjunction with standard risk factors for death and cardiovascular disease (CVD). However, the field of arterial stiffness investigation, which has exploded over the past 20 years, has proliferated without logistical guidance for clinical and …

Recommendations for Improving and Standardizing Vascular Research on Arterial Stiffness: A Scientific Statement From the American Heart Association

In the past five years, skeletal muscle has emerged as a paradigm of “nitric oxide” (NO) function and redox-related signaling in biology. All major nitric oxide synthase (NOS) isoforms, including a muscle-specific splice variant of neuronal-type (n) NOS, are expressed in skeletal muscles of all mammals. Expression and localization of NOS isoforms are dependent on age and developmental stage, innervation and activity, history of exposure to cytokines and growth factors, and muscle fiber type and species. nNOS in particular may show a fast-twitch muscle predominance. Muscle NOS localization and activity are regulated by a number of protein-protein interactions and co- and/or posttranslational modifications. Subcellular compartmentalization of the NOSs enables distinct functions that are mediated by increases in cGMP and byS-nitrosylation of proteins such as the ryanodine receptor-calcium release channel. Skeletal muscle functions regulated by NO or related molecules include force production (excitation-cont...

Physiology of Nitric Oxide in Skeletal Muscle

The vascular myogenic response refers to the acute reaction of a blood vessel to a change in transmural pressure. This response is critically important for the development of resting vascular tone, upon which other control mechanisms exert vasodilator and vasoconstrictor influences. The purpose of this review is to summarize and synthesize information regarding the cellular mechanism(s) underlying the myogenic response in blood vessels, with particular emphasis on arterioles. When necessary, experiments performed on larger blood vessels, visceral smooth muscle, and even striated muscle are cited. Mechanical aspects of myogenic behavior are discussed first, followed by electromechanical coupling mechanisms. Next, mechanotransduction by membrane-bound enzymes and involvement of second messengers, including calcium, are discussed. After this, the roles of the extracellular matrix, integrins, and the smooth muscle cytoskeleton are reviewed, with emphasis on short-term signaling mechanisms. Finally, suggestions are offered for possible future studies.

https://www.physiology.org/doi/pdf/10.1152/physrev.1999.79.2.387

Signaling mechanisms underlying the vascular myogenic response

ACE inhibitors have achieved widespread usage in the treatment of cardiovascular and renal disease. ACE inhibitors alter the balance between the vasoconstrictive, salt-retentive, and hypertrophic properties of angiotensin II (Ang II) and the vasodilatory and natriuretic properties of bradykinin and alter the metabolism of a number of other vasoactive substances. ACE inhibitors differ in the chemical structure of their active moieties, in potency, in bioavailability, in plasma half-life, in route of elimination, in their distribution and affinity for tissue-bound ACE, and in whether they are administered as prodrugs. Thus, the side effects of ACE inhibitors can be divided into those that are class specific and those that relate to specific agents. ACE inhibitors decrease systemic vascular resistance without increasing heart rate and promote natriuresis. They have proved effective in the treatment of hypertension, they decrease mortality in congestive heart failure and left ventricular dysfunction after myocardial infarction, and they delay the progression of diabetic nephropathy. Ongoing studies will elucidate the effect of ACE inhibitors on cardiovascular mortality in essential hypertension, the role of ACE inhibitors in patients without ventricular dysfunction after myocardial infarction, and the role of ACE inhibitors compared with newly available angiotensin AT1 receptor antagonists.

Angiotensin-Converting Enzyme Inhibitors

Control of resistance, exchange, and capacitance functions in the peripheral circulation

During 6 min exercise on a bicycle ergometer the volume of the leg in normal males increased so as to indicate, after correction for increased regional blood volume, an average trans-capillary fluid loss into the leg muscles of 19, 31, and 45 ml/kg tissue at light (300 kpm/min), moderate (900 kpm/min), and heavy (1200–1500 kpm/min) work load. The total fluid loss into the active muscle mass was calculated to comprise about 1100 ml during heavy work. Since the concomitant decrease of plasma volume was 600 ml, it follows that some 500 ml of fluid must have entered the circulatory system during the work. The study indicated that this compensatory fluid gain was accomplished by absorption of extravascular fluid from inactive tissues and partly caused by osmosis resulting from work induced arterial hyperosmolality (average increase 22 mOsm/kg H2O). Fluid absorption from inactive tissues was studied in experimental animals during exercise and in resting humans during arterial hyperosmolality produced by intravenous hypertonic infusions. The investigations suggested that at least half of the fluid gain to the circulatory system in heavy exercise could be ascribed to the increased arterial osmolality and the remainder to a reflex decrease of capillary pressure.

Fluid transfer between blood and tissues during exercise.

When a vascular bed is exposed to an increased transmural pressure, as occurs in the lower extremities in man on standing, adjustments of the vascular tone take place which tend to protect the organism against excessive transcapillary loss of circulating fluid into the extravascular space. Thus, first, by closure of a number of the precapillary sphincter vessels, the size of the capillary surface area directly available for blood flow and hence for fluid exchange is reduced, and the rate of filtration correspondingly decreased. Second, by an increase of the ratio of precapillary to postcapillary flow resistance which increases the pressure drop across the precapillary resistance vessels, the rise in capillary pressure will be less than expected from the observed increase in arterial and venous pressures. From a quantitative point of view, the reduction of the capillary surface area seems to be by far the more important protective mechanism, as it was shown that in the human foot the rate of filtration per unit transcapillary pressure difference was decreased to only 1/3 to 1/8 of normal when the regional transmural pressure was increased by shifting from the supine to the erect posture.

The vascular rejponse parterns described are evidently brought into play mainly by a reinforcement of the local inherent automaticity of the vascular smooth muscle induced by the raised trans. nura1 pressure, but, in all probability, can be intensified to some extent by superimpored extrinsic vasomotor fiber influence. This active vascular adaptation to hydrostatic load seems to be of greater importance than extravaicular mechanisms for preventing edema formation in dep-ndent regions in normal subjects during quiet standing.

Vascular Adjustments to Increased Transmural Pressure in Cat and Man with Special Reference to Shifts in Capillary Fluid Transfer

Background The results of a recent meta-analysis aroused concern about an increased risk of death associated with the use of paclitaxel-coated angioplasty balloons and stents in lower-limb...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2005206?articleTools=true

Stefan Mellander

Papers

Control of resistance, exchange, and capacitance functions in the peripheral circulation

Fluid transfer between blood and tissues during exercise.

Vascular Adjustments to Increased Transmural Pressure in Cat and Man with Special Reference to Shifts in Capillary Fluid Transfer

Mortality with Paclitaxel-Coated Devices in Peripheral Artery Disease.

The effect of graded vasoconstrictor fibre stimulation on the intestinal resistance and capacitance vessels.