The survival and well-being of all species requires appropriate physiological responses to environmental and homeostatic challenges. The re-establishment and maintenance of homeostasis entails the coordinated activation and control of neuroendocrine and autonomic stress systems. These collective stress responses are mediated by largely overlapping circuits in the limbic forebrain, the hypothalamus and the brainstem, so that the respective contributions of the neuroendocrine and autonomic systems are tuned in accordance with stressor modality and intensity. Limbic regions that are responsible for regulating stress responses intersect with circuits that are responsible for memory and reward, providing a means to tailor the stress response with respect to prior experience and anticipated outcomes.

Neural regulation of endocrine and autonomic stress responses.

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

The cardiovascular and other actions of angiotensin II (Ang II) are mediated by AT(1) and AT(2) receptors, which are seven transmembrane glycoproteins with 30% sequence similarity. Most species express a single autosomal AT(1) gene, but two related AT(1A) and AT(1B) receptor genes are expressed in rodents. AT(1) receptors are predominantly coupled to G(q/11), and signal through phospholipases A, C, D, inositol phosphates, calcium channels, and a variety of serine/threonine and tyrosine kinases. Many AT(1)-induced growth responses are mediated by transactivation of growth factor receptors. The receptor binding sites for agonist and nonpeptide antagonist ligands have been defined. The latter compounds are as effective as angiotensin converting enzyme inhibitors in cardiovascular diseases but are better tolerated. The AT(2) receptor is expressed at high density during fetal development. It is much less abundant in adult tissues and is up-regulated in pathological conditions. Its signaling pathways include serine and tyrosine phosphatases, phospholipase A(2), nitric oxide, and cyclic guanosine monophosphate. The AT(2) receptor counteracts several of the growth responses initiated by the AT(1) and growth factor receptors. The AT(4) receptor specifically binds Ang IV (Ang 3-8), and is located in brain and kidney. Its signaling mechanisms are unknown, but it influences local blood flow and is associated with cognitive processes and sensory and motor functions. Although AT(1) receptors mediate most of the known actions of Ang II, the AT(2) receptor contributes to the regulation of blood pressure and renal function. The development of specific nonpeptide receptor antagonists has led to major advances in the physiology, pharmacology, and therapy of the renin-angiotensin system.

https://pharmrev.aspetjournals.org/content/pharmrev/52/3/415.full.pdf

International Union of Pharmacology. XXIII. The Angiotensin II Receptors

It is increasingly apparent that not only is a cure for the current worldwide diabetes epidemic required, but also for its major complications, affecting both small and large blood vessels. These complications occur in the majority of individuals with both type 1 and type 2 diabetes. Among the most prevalent microvascular complications are kidney disease, blindness, and amputations, with current therapies only slowing disease progression. Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a major risk factor for macrovascular complications, such as heart attacks and strokes. There have been a large number of new therapies tested in clinical trials for diabetic complications, with, in general, rather disappointing results. Indeed, it remains to be fully defined as to which pathways in diabetic complications are essentially protective rather than pathological, in terms of their effects on the underlying disease process. Furthermore, seemingly independent pathways are also showing significant interactions with each other to exacerbate pathology. Interestingly, some of these pathways may not only play key roles in complications but also in the development of diabetes per se. This review aims to comprehensively discuss the well validated, as well as putative mechanisms involved in the development of diabetic complications. In addition, new fields of research, which warrant further investigation as potential therapeutic targets of the future, will be highlighted.

Mechanisms of Diabetic Complications

https://www.psychologie.uni-freiburg.de/abteilungen/psychobio/team/publikationen/BiolPsychiatry-MH03.pdf

Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress

https://www.amherst.edu/media/view/143475/original/green_2001_biological-psychiatry.pdf

Oxytocin and autistic disorder: alterations in peptide forms.

Previous work demonstrated that oxytocinergic projections to the solitary vagal complex are involved in the restraint of exercise-induced tachycardia (2). In the present study, we tested the idea t...

Baroreflex control of heart rate by oxytocin in the solitary-vagal complex

Experiments were performed to investigate the influence of exercise training on cardiovascular function in mice. Heart rate, arterial pressure, baroreflex sensitivity, and autonomic control of hear...

https://www.physiology.org/doi/pdf/10.1152/japplphysiol.00870.2003

Exercise training changes autonomic cardiovascular balance in mice

Objective To investigate the effect of fructose consumption on the light/dark pattern of blood pressure, heart rate and autonomic neural function in mice. Background Insulin resistant diabetes is associated with hypertension and autonomic dysfunction. There is evidence that the increasing incidence of diabetes may be related to dietary changes, including consumption of high levels of fructose. Design/methods C57/BL mice, instrumented with radiotelemetric arterial catheters, were fed a control or high fructose diet (60%). Cardiovascular parameters measured were light/dark pattern of mean arterial pressure (MAP), heart rate (HR) and variability (time and frequency domain). We also measured plasma insulin, glucose, lipids and angiotensin II (Ang II) as well as glucose tolerance. In situ hybridization was used to measure brainstem expression of tyrosine hydroxylase (TH) and Ang AT1a mRNA. Results Fructose diet (8 weeks) produced an increase in MAP, variance and low frequency domain (14 ± 3 vs. 33 ± 4 mm Hg 2 , variance and 10 ± 2 vs. 26 ± 4 mm Hg 2 , LF, control vs. fructose, P P P 1 -adrenergic blockade with prasozin were augmented in fructose-fed mice. Using quantitative in situ hybridization, we found that Ang AT1a receptor and TH mRNA expression were significantly increased in the brainstem locus coeruleus. Conclusion A high fructose diet in mice produced nocturnal hypertension and autonomic imbalance which may be related to activation of sympathetic and angiotensin systems.

Nocturnal hypertension in mice consuming a high fructose diet.

The circadian pattern of mean arterial pressure (MAP) and heart rate (HR) was measured in C57BL mice with carotid arterial catheters. Cardiovascular parameters were recorded continuously with a com...

Mariana Morris

Papers

Oxytocin and autistic disorder: alterations in peptide forms.

Baroreflex control of heart rate by oxytocin in the solitary-vagal complex

Exercise training changes autonomic cardiovascular balance in mice

Nocturnal hypertension in mice consuming a high fructose diet.

Circadian blood pressure and heart rate rhythms in mice