Prejunctional Dopamine Receptor Stimulants
M.D. Francesco Amenta in Peripheral Dopamine Pathophysiology, 2019
Prejunctional dopamine (DA) receptor stimulation explains both the global effects of N-N-di-n-Propyl DA (DPDA) on blood pressure and heart rate and the hind limb vasodilation observed in the cat or dog during intravenous or local intra-arterial infusions. The composite data provided by animal studies with DPDA suggest that an orally effective prejunctional DA receptor stimulant might have clinical utility in the treatment of hypertension and congestive cardiac failure, with potential advantages over certain other agents in not having the potential to produce orthostasis or heart rate increases. Evidence supporting an effect of bromocriptine on prejunctional dopamine receptors located on nerves supplying vascular smooth muscle is convincing. Prejunctional DA2 receptor stimulation by bromocriptine or co-dergocrine reduces plasma noradrenaline levels but has no influence on basal plasma renin activity in normotensive subjects, or patients with hypertension or congestive cardiac failure. A great many compounds have been shown to exert potent, long-lasting stimulant effects on prejunctional DA2 receptors.
Skin Morphology, Development and Physiology
Heather A.E. Benson, Michael S. Roberts, Vânia Rodrigues Leite-Silva, Kenneth A. Walters in Cosmetic Formulation, 2019
Heat regulation occurs through the use of the subcutaneous fat pad, physiological regulation of blood flow to effect for instance, heat loss by vasodilation and cooling by perspiration. Blood flow changes are most evident in the skin in relation to various physiological responses and include psychological effects such as shock and embarrassment, temperature effects and physiological responses to exercise, haemorrhage, and alcohol consumption. This chapter introduces the reader to the basic morphology of skin, outlines the stages in the development of the barrier layer, explains the major proteins of the stratum corneum and to illustrate repair mechanisms following barrier disruption. The entire process of epidermal terminal differentiation is geared towards the generation of the specific chemical morphology of the stratum corneum. Thus, the end products of this process are the intracellular protein matrix and the intercellular lipid lamellae. Certainly, epidermal stem cells are located in the basal epidermis and also in the hair follicles and sebaceous glands.
Hyperglycemia Impairs Blood Vessel Function
Robert Fried, Richard M. Carlton in Type 2 Diabetes, 2018
This chapter describes the steady process whereby oxidative stress leads to Type 2 diabetes, and damages vascular endothelium, by causing loss of nitric oxide (NO) synthesis. This loss results in both micro- and macrovessel damages as commonly seen in neuro- and vasculopathies present in many organs ranging from the eyes to the kidneys. The chapter also cites the evidence for endoplasmic reticulum, and mitochondrial stress in vasculopathies resulting from oxidative stress. Here also is a detailed discussion of various means of analysis permitting evaluation of damage due to diabetes. These include clinical correlates of arterial pulse waveform, and velocity, and flow-mediated vasodilation and reactive hyperemia.
Prolonged Local Forearm Hyperinsulinemia Induces Sustained Enhancement of Nitric Oxide–Dependent Vasodilation in Healthy Subjects
Published in Endothelium, 2004
Thomas S. Hermann, Nikolaj Ihlemann, Helena Dominguez, Christian Rask-Madsen, Lars Kober, Christian Torp-Pedersen
Systemic hyperinsulinemia induces enhancement of endothelium-dependent vasodilation of healthy subjects. During systemic infusion of insulin, endothelium-dependent vasodilation may be improved through a decrease in the concentration of free fatty acids. To explore the direct effect of continued insulin on the vascular endothelium, the authors infused insulin in the brachial artery for 4 h and measured the effect on endothelium-dependent vasodilation in the human forearm. Thirty-six experiments were performed in healthy subjects, mean age 47.7 ± 1.1 years. Endotheliumdependent and -independent vasodilatation was studied during intra-arterial infusion of serotonin and sodium nitroprusside (SNP), respectively. Forearm blood flow was measured by plethysmography. Intra-arterial insulin was infused for 240 min at a constant rate and blood flow was measured hourly during stimulation of endothelium-dependent and -independent vasodilation. NGmonomethyl-L-arginine (L-NMMA) was coinfused to test the degree of nitric oxide (NO)-mediated vasodilation. Insulin infusion for 60 min enhanced serotonin-induced vasodilation by 37% compared to vehicle, p = · 016. This increase was maintained for 4 h and was blocked by L-NMMA. The SNP response was increased by insulin but the increment was inhibited by L-NMMA. Four hours of local forearm hyperinsulinemia causes a sustained increase in endothelium dependent vasodilation in resistance vessels, which is mediated by NO.
Role of endothelium-derived vasodilators and K+ channels in ischemic vasodilation of guinea-pig choroidal arterioles
Published in Current Eye Research, 1999
Kazushi Tamai, Hikaru Suzuki, Shoichiro Shirai, Yuichiro Ogura
PURPOSE. To assess the roles of endothelium-derived vasodilators and K + channels on metabolic ischemia-induced vasodilation from diameter changes in choroidal arterioles of the guinea-pig. METHODS. The choroid was isolated from the guinea-pig eye-ball, pinned flat on a silicone rubber plate, and superfused with oxygenated warmed (35°C) Krebs solution. Diameters of choroidal arterioles were measured using video microscopy and a computer program for analysis. Vasodilatory effects were examined after the choroid was exposed to glucose-free/NaCN solutions for 10 minutes. The effects of N?-nitro-L-arginine (nitroarginine), indomethacin, and K + channel inhibitors (glibenclamide [Glib] and charybdotoxin [ChTX]) on ischemic vasodilation were assessed. RESULTS. Reversible vasodilation was observed when the choroid was exposed to glucose-free/NaCN (10 -3 M) solutions. Nitroarginine (10 -4 M), Glib (2×10 -5 M) and ChTX (10 -7 M) significantly inhibited glucose-free/NaCN (10 -3 M)-induced vasodilation by 47%, 62%, and 24%, respectively. No significant inhibitory effect was observed with indomethacin (10 -5 M). Simultaneous application of Glib and ChTX reduced vasodilation by 77%. When Glib and ChTX were added together to nitroarginine, dilation was reduced by 86%. With high K + ([K]o = 47.2 mM) Krebs solution, ischemia caused a slight vasodilation (11%), which was significantly inhibited by nitroarginine. CONCLUSIONS. In guinea-pig choroidal arterioles, glucose-free/ NaCN-induced ischemic vasodilation was mainly mediated by NO and K ATP channels. A part of NO-mediated vasodilation was induced independent of the opening of K + channels.
Impaired Coronary Microvascular Dilation Correlates with Enhanced Vascular Smooth Muscle MLC Phosphorylation in Diabetes
Published in Microcirculation, 2009
Richard T. Clements, Neel R. Sodha, Jun Feng, Munir Boodhwani, Yuhong Liu, Shigetoshi Mieno, Kamal R. Khabbaz, Cesario Bianchi, Frank W. Sellke
Objective: Impaired endothelium-independent vasodilation is a known consequence of types 1 and 2 diabetes, and the mechanism of impaired vasodilation is not well understood. The following study investigated the effects of types 1 and 2 diabetes in endothelial-independent vasodilation associated with coronary vascular smooth muscle (VSM) relaxation and contractile signaling mechanisms. Materials and Methods: Type 1 diabetes was induced in Yucatan miniswine via alloxan injection and treated with or without insulin (DM and IDM). Nondiabetic swine served as controls (ND). Expression and/or phosphorylation of determinants of VSM relaxation and contraction signaling were examined in coronary arteries and microvessels. Coronary microvessel relaxation was assessed by using sodium nitroprusside (SNP). In addition, SNP-induced vasodilation and myosin light-chain (MLC) phosphorylation was determined in coronary microvessels isolated from ND and type 2 diabetic human atrial appendage. Results: Diabetic impairment in SNP-induced relaxation was completely normalized by insulin. Soluble guanylate cyclase (sGC) VSM expression decreased in both DM and IDM groups and did not correlate with vasorelaxation. Phosphorylation of MLC and myosin phosphatase increased in the DM group and MLC phosphorylation strongly correlated with impaired VSM relaxation (r=0.670, P