Regulation of Blood Pressure is Impacted by Serum Cholesterol

Joseph Wilson^*
*Correspondence: Joseph Wilson, Department of Clinical and Experimental Medicine, Federico II University, Naples, Italy, Email:

Introduction

Cardiovascular disease is the leading cause of morbidity and mortality worldwide, and high blood pressure is a significant risk factor for this condition. In developed nations; hypertension is the leading cause of disability-adjusted life years and the leading cause of mortality. Hypertension is a polygenic and complex disease that is becoming more common.Endothelial dysfunction, increased renin-angiotensin system (RAS) activity, and sympathetic nervous system (SNS) hyperactivation have been considered important risk factors for hypertension and hint at important events taking place at the interface of the endothelium, kidney, and SNS. Europe has a higher prevalence of hypertension than North America, and two thirds of those people live in developing countries. Mechanistically, endothelial dysfunction, increased renin-angiotensin system (RAS) activity, and sympathetic nervous system (SNS) hyperactivation have been considered as important risk factors of hypertension and hint at important events taking place at the interface of the endothelium, kidney, and SNS. Obesity affects both children and adults worldwide. According to the National Health and Nutrition Examination Survey III, body mass index is an independent risk factor for hypertension, independent of age, sex, race, and smoking. A long-term weight/hypertension relationship study showed that weight loss of 10 kg is associated with a significant decrease in both diastolic and systolic blood pressure. Obesity and hypertension are two complex disorders that are closely interrelated, but the precise underlying association remains elusive [1].

The primary characteristic of obesity is the uncontrolled expansion of adipose tissue. The view of adipose tissue has transformed from an inert energy store to the largest endocrine organ in the last two decades. Adipose tissue secretes a variety of hormones, including leptin, adiponectin, resistin, visfatin, tumor necrosis factor-, interleukin-6, and others. Leptin, resistin, tumor necrosis factor-, and interleukin-6 secretion has been linked to insulin resistance and the development of inflammation in obese individuals. Adiponectin is the only hormone that exhibits the opposite pattern. Adiponectin levels have been linked to insulin sensitization, glucose use, oxidation, cardiovascular protection, and insulin sensitization. Adiponectin may also play a role in the development of hypertension. Ohashi et al. found that, regardless of insulin resistance, adiponectin-deficient animals had significantly higher systolic blood pressure than wild-type control animals on a high-salt diet. Normal blood pressure was restored after adenoviral infection restored adiponectin expression. In genetically obese KKAy mice, overexpression of adiponectin can also lower systolic blood pressure. However, despite the well-established association of adiponectin with metabolic disorders and cardiovascular disease, very few studies address the relationship between adiponectin and hypertension at a mechanistic level. Recently, several studies have focused on the effects of adiponectin on the endothelium, kidney, and SNS. These studies show that hypoadiponectinemia is a risk factor for hypertension independent of insulin resistance and diabetes. The association between adipoAdiponectin: The impact of other fat-derived hormones on hypertension is discussed elsewhere. Here, we discuss these findings as they pertain specifically to adiponectin.A complex secretory molecule that only comes from adipose tissue; adiponectin (also known as Acrp30/adipoQ/apM1/GBP28) is a 30-kDa molecule that has three distinct domains. The hypervariable region at the N terminus is frequently utilized as the antigenic site for the generation of antibodies that are specific to a specific species. The globular domain at the C terminus of adiponectin is followed by the collagenous stalk, which has 22 GXY repeats. Adiponectin is found both inside and outside of cells in at least three different higher-order complexes: form with a high molecular weight, a hexamer of low molecular weight, and a trimeric form. The total level and HMW ratio are decreased in obese patients and obese mouse models suggesting that adiponectin, particularly the HMW form, may be involved in obesity-related disorders. Numerous studies have demonstrated that the various complexes perform distinct functions and that the ratio of HMW to the other forms serves as an independent predicting factor for metabolic disorder [2-4].

The receptors have been identified ten years after adiponectin was discovered. Yamauchi et al. used expression cloning to isolate two related receptors from human skeletal muscle. Despite being the products of distinct genes, these receptors share a sequence identity of 67%. While AdipoR2 is only found in the liver, AdipoR1 is expressed and enriched more frequently in muscle.AdipoR1 and AdipoR2 have been shown to be essential mediators for adiponectin signaling in both in vitro and in vivo studies. AdipoR1 mediates glucose uptake, -oxidation, and peroxisome proliferator-activated receptor (PPAR) activation in skeletal muscle, as demonstrated by in vitro knockdown experiments. AdipoR1 affects gluconeogenesis by raising AMPK activity in the liver. AdipoR2 is also involved in scavenging reactive oxygen species, activating the nuclear receptor PPAR, and its downstream target genes, which mediate -oxidation. AdipoR1 signaling's intracellular aspects have also been clarified. Mao et al. discovered that the intracellular fragment of AdipoR1 interacts with APPL1, an adaptor molecule with a plecktrin homology domain and a phosphotyrosine binding domain. The phosphotyrosine binding domain is required for this interaction, but tyrosine phosphorylation is not. The widespread expression of APPL1 may indicate the widespread significance of adiponectin signaling in various tissues. On the other hand, APPL1 might also interact with other receptors. Overexpression of APPL1 in vitro has been shown to increase glucose uptake, oxidation, and AMPK activation triggered by adiponectin. The crosstalk between adiponectin signaling and the insulin signal transduction cascade may also involve APPL1. This could imply that the same adaptor molecule can help these two hormones work together [5].

Adiponectin and Endothelial Dysfunction The endothelium is a major paracrine organ that controls vascular tone, inflammation, and smooth muscle cell proliferation. It also serves as the inert interface between the circulating blood and the vessel wall. Under normal conditions, NO is thought to be the mediator for vasoconstriction and vasodilation, adhesion molecule expression and leukocyte transmigration, and control of smooth muscle cell growth. The availability of substrates and cofactors, transcription of eNOS, mRNA stability of eNOS, subcellular localization of eNOS protein, enzymatic uncoupling, and posttranslational modifications all play a role in regulating the activity of endothelial NO synthase (eNOS) and NO production. Recently, a growing body of evidence suggests that endothelial dysfunction is linked to hypoadiponectinemia. Ouchi et al. discovered that an endothelial vasodilation response is correlated with plasma adiponectin levels by measuring forearm blood flow in response to reactive hyperemia. Adiponectin-deficient mice demonstrated impaired endothelium-dependent vasodilation and NO production in animal studies and Tan et al. demonstrated that diabetic patients with hypoadiponectinemia have a lower vasodilation response. A similar gathering found that adiponectin organization expands NO creation in human aortic endothelial cells. Ohashi et al. demonstrated that, following high-salt feeding, adiponectin knockout mice had lower levels of nitrate and nitrite than their wild-type littermates. Adiponectin expression and secretion decrease as a result of the obesity-associated metabolic syndrome. One of the most important mediators of obesity-associated NO decrease, endothelial dysfunction, and cardiovascular disease may be the dysregulated production of adiponectin. Adiponectin and the RAS Through angiotensin II signaling, the RAS regulates blood pressure and extracellular volume. However, in pathophysiological conditions like obesity-associated metabolic diseases, the overproduction of angiotensin II contributes significantly to the onset and progression of comorbid conditions like hypertension and insulin resistance [3].

Clinical studies are showing that angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers can lower blood pressure in hypertensive patients by blocking RAS. This is consistent with the significant role that RAS plays in controlling blood pressure. Angiotensin II receptor blockers, on the other hand, have been shown in recent clinical trials to have beneficial effects beyond blood pressure control, including insulin sensitization, cardiac protection, and anti-diabetes. Animal studies have also shown that angiotensin II signaling is involved in diabetes and insulin resistance. Acute treatment with irbesartan, an angiotensin II receptor blocker, for one hour significantly increases glucose uptake and glucose elimination throughout the body in Zucker rats with insulin resistance genes. Another study using diet-induced, insulin-resistant animals found similar effects after angiotensin II receptor antagonist treatment. Oral treatment with olmesartan, an angiotensin II receptor blocker, showed effects on insulin sensitization that were hypertension-independent. The experimental group showed higher glucose uptake, improved glucose tolerance, and insulin sensitization during a chronic treatment for three weeks [4].

The deep rooted job of adiponectin as an insulin sensitizer incited further examinations into the connection between angiotensin II receptor obstructing and adiponectin creation. Adiponectin levels in the bloodstream rise after exposure to angiotensin II receptor blockers, according to increasing evidence from clinical studies. Losartan significantly increased the level of adiponectin, whereas amlodipine did not, despite similar blood pressure control, according to Watanabe et al. The angiotensin II receptor blocker–mediated increase of adiponectin may contribute to the additional beneficial effects that these drugs exhibit in hypertensive patients. Angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker administration showed increased adiponectin levels compared with other common antihypertensive drugs. Several mechanisms have been proposed to explain the stimulatory effect of angiotensin II receptor blocking on circulating adiponectin levels in a study comparing antihypertensive drugs for their impact on adiponectin regulation. Angiotensin II receptor blockers may elicit their effect by inhibiting angiotensin II receptor subtype 1 signaling, as angiotensin II inhibits adiponectin production through angiotensin II receptor subtype. A two-week angiotensin II infusion significantly reduces circulating levels of adiponectin in rats. An antagonist or an agonist of angiotensin II receptor subtype 2 treatment has no effect on angiotensin II's suppression of adiponectin. Interestingly, angiotensin II infusion decreases adiponectin before raising blood pressure. Further research with adiponectin-deficient animals and angiotensin II infusion will be required to clarify the role of adiponectin in angiotensin II-induced hypertension [5].

Conclusion

The prevalence of hypertension and obesity continues to rise. Both conditions are major risk factors for cardiovascular disease, which is the leading cause of death and morbidity worldwide. Numerous mechanisms, including endothelial dysfunction, RAS hyperactivation, SNS overdrive, and impairment of renal-pressure natriuresis73, may contribute to obesity-induced hypertension. A substantial body of evidence suggests that decreased adiponectin levels act as a mediator of some of these effects. As a result, the primary link to obesity-associated hypertension may be the downregulation of adiponectin caused by obesity. Clinical studies show that antihypertensive medications may have pleiotropic effects, such as controlling blood pressure, controlling diabetes, and protecting the heart. It has been hypothesized that adiponectin, which is only secreted by adipose tissue, lowers the risk of insulin resistance, inflammation, type 2 diabetes, and cardiovascular disease. Adiponectin levels rise following treatment with a subset of antihypertensive medications, suggesting that these beneficial effects may partially mediate.

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