5-Hydroxytryptamine may be a viable treatment option for hypertension resistant to diuretic treatment.

Serotonin (5-hydroxytryptamine, 5-HT) causes a sustained reduction in mean arterial pressure (MAP) during chronic (one week) infusion in both normo- and hypertensive rats. We hypothesized that the hypotensive effect of 5-HT will remain intact in male Dahl-SS rats that are unresponsive to a diuretic. Male Dahl-SS rats on a normal or 4% NaCl diet were instrumented with radiotelemeters for blood pressure measurement.

Sympathetic nerves are sparsely distributed in rat mesenteric perivascular adipose tissue.

Perivascular adipose tissue (PVAT) importantly affects the contractile function of conduit and resistance arteries. Some findings suggest that this effect of PVAT is controlled in part by sympathetic neural input directly to various PVAT depots. However, the degree of innervation of PVAT by the sympathetic nervous system remains in question.

The 5-HT7 receptor contributes to increased hindquarter blood flow caused by skeletal muscle contraction.

Serotonin (5-hydroxytryptamine, 5-HT) at low plasma concentrations reduces blood pressure and dilates some skeletal muscle arterioles in the rat. We hypothesized that the 5-HT7 receptor is essential for both 5-HT-induced changes in blood pressure and skeletal muscle arteriolar function. Male 5-HT7 receptor knock out (KO) rats under isoflurane anesthesia had a higher resting hindquarter vascular resistance [HQVR; mm Hg/ml/min; KO (16.

Single-nucleus analysis of thoracic perivascular adipose tissue reveals critical changes in cell composition, communication, and gene regulatory networks induced by a high fat hypertensive diet.

Cardiovascular disease (CVD) is the leading cause of death worldwide, with hypertension being its primary causal factor. Most blood vessels are surrounded by perivascular adipose tissue (PVAT), which regulates blood vessel tone through the secretion of vasoactive factors. PVAT is recognized as a key mediator of vascular function and dysfunction in CVD, although the underlying mechanisms remain poorly understood.

β-arrestin biased signaling is not involved in the hypotensive actions of 5-HT receptor stimulation: use of Serodolin.

The 5-hydroxytryptamine 7 receptor (5-HT) is necessary for 5-HT to cause a concentration-dependent vascular relaxation and hypotension. 5-HT is recognized as having biased signaling, transduced through either Gs or β -arrestin. It is unknown whether 5-HT signals in a biased manner to cause vasorelaxation/hypotension.

Perivascular Adipose Tissue Remodels Only after Elevation of Blood Pressure in the Dahl SS Rat Fed a High-Fat Diet.

Introduction: Tunica media extracellular matrix (ECM) remodeling is well understood to occur in response to elevated blood pressure, unlike the remodeling of other tunicas. We hypothesize that perivascular adipose tissue (PVAT) is responsive to hypertension and remodels as a protective measure.

Methods: The adventitia and PVAT of the thoracic aorta were used in measuring ECM genes from 5 pairs of Dahl SS male rats on 8 or 24 weeks of feeding from weaning on a control (10% Kcal fat) or high-fat (HF; 60%) diet.

Renal and hypothalamic inflammation in renovascular hypertension: role of afferent renal nerves.

Renal denervation (RDN) is a potential therapy for drug-resistant hypertension. However, whether its effects are mediated by ablation of efferent or afferent renal nerves is not clear. Previous studies have implicated that renal inflammation and the sympathetic nervous system are driven by the activation of afferent and efferent renal nerves.

Chemerin is resident to vascular tunicas and contributes to vascular tone.

The adipokine chemerin may support blood pressure, evidenced by a fall in mean arterial pressure after whole body antisense oligonucleotide (ASO)-mediated knockdown of chemerin protein in rat models of normal and elevated blood pressure. Although the liver is the greatest contributor of circulating chemerin, liver-specific ASOs that abolished hepatic-derived chemerin did not change blood pressure. Thus, other sites must produce the chemerin that supports blood pressure.

5-HT receptors mediate dilation of rat cremaster muscle arterioles in vivo.

Objective: Serotonin (5-HT) infusion in vivo causes hypotension and a fall in total peripheral resistance. However, the vascular segment and the receptors that mediate this response remain in question. We hypothesized that 5-HT receptors mediate arteriolar dilation to 5-HT in skeletal muscle microcirculation.

Skin Vascular Resistance Decreases during 5-HT-Induced Hypotension in the Rat.

A recognized vasodilator, the infusion of 5-hydroxytryptamine (5-HT, serotonin) decreases blood pressure through the reduction of total peripheral resistance in the rat. It is not clear which vascular beds/tissues are responsible for this fall. We hypothesized that an increase in blood flow within the skin, measured as an elevated temperature (T) in the thermoregulatory tail and paws, enables at least part of 5-HT-induced reduction in blood pressure through active vasodilation.

A high fat diet does not stimulate blood pressure dependence on chemerin in the Sprague-Dawley rat.

Unlabelled: The adipokine chemerin is a candidate for connecting obesity to hypertension.

Study Objective: To test the hypothesis that a high fat (HF) diet stimulates dependence on chemerin for blood pressure regulation.

Design: Blood pressure in male Sprague Dawley rats fed a control (10 % fat) or HF (60 % fat) diet from weaning was measured using radiotelemetry.

Reduction in Hindquarter Vascular Resistance Supports 5-HT Receptor Mediated Hypotension.

The 5-HT receptor is the primary mediator of both the ( View Article and Find Full Text PDF

Male and female high-fat diet-fed Dahl SS rats are largely protected from vascular dysfunctions: PVAT contributions reveal sex differences.

Vascular dysfunctions are observed in the arteries from hypertensive subjects. The establishment of the Dahl salt-sensitive (SS) male and female rat models to develop a reproducible hypertension with high-fat (HF) diet feeding from weaning allows addressing the question of whether HF diet-associated hypertension results in vascular dysfunction similar to that of essential hypertension in both sexes. We hypothesized that dysfunction of three distinct vascular layers, i.

Phenotypic Changes in T Cell and Macrophage Subtypes in Perivascular Adipose Tissues Precede High-Fat Diet-Induced Hypertension.

Perivascular adipose tissue (PVAT) may connect adiposity to hypertension because of its vasoactive functions and proximity to blood vessels. We hypothesized that immune cell changes in PVATs precede the development of high fat diet (HFD)-induced hypertension. Both sexes of Dahl S rat become equally hypertensive when fed a HFD.

Renal Denervation and Celiac Ganglionectomy Decrease Mean Arterial Pressure Similarly in Genetically Hypertensive Schlager (BPH/2J) Mice.

Renal denervation (RDNX) lowers mean arterial pressure (MAP) in patients with resistant hypertension. Less well studied is the effect of celiac ganglionectomy (CGX), a procedure which involves the removal of the nerves innervating the splanchnic vascular bed. We hypothesized that RDNX and CGX would both lower MAP in genetically hypertensive Schlager (BPH/2J) mice through a reduction in sympathetic tone.

Vascular reactivity stimulated by TMA and TMAO: Are perivascular adipose tissue and endothelium involved?

Trimethylamine (TMA), formed by intestinal microbiota, and its Flavin-Monooxygenase 3 (FMO3) product Trimethylamine-N-Oxide (TMAO), are potential modulators of host cardiometabolic phenotypes. High circulating levels of TMAO are associated with increased risk for cardiovascular diseases. We hypothesized that TMA/TMAO could directly change the vascular tone.

Activation of the 5-HT receptor but not nitric oxide synthase is necessary for chronic 5-hydroxytryptamine-induced hypotension.

New Findings: What is the central question of this study? What mechanisms account for the hypotension observed during chronic elevations in circulating 5-hydroxytryptamine in rats? What is the main finding and its importance? Chronic 5-hydroxytryptamine-induced hypotension requires continued activation of the 5-HT receptor subtype but does not require NO, an outcome that resolves previous conflicting results. Therapeutic interruption of the hypotensive actions of 5-HT under pathophysiological conditions can only be achieved through blockade of the 5-HT receptor.

Abstract: Low dose infusion of 5-hydroxytryptamine (5-HT) to rats causes both an acute and a chronic fall in arterial blood pressure.

Blood pressure changes PVAT function and transcriptome: use of the mid-thoracic aorta coarcted rat.

Perivascular adipose tissue (PVAT) modifies the contractile function of the vessel it surrounds (outside-in signaling). Little work points to the vessel actively affecting its surrounding PVAT. We hypothesized that inside-out arterial signaling to PVAT would be evidenced by the response of PVAT to changes in tangential vascular wall stress.

Potential role of intermittent functioning of baroreflexes in the etiology of hypertension in spontaneously hypertensive rats.

The spontaneously hypertensive rat (SHR) is a genetic model of primary hypertension with an etiology that includes sympathetic overdrive. To elucidate the neurogenic mechanisms underlying the pathophysiology of this model, we analyzed the dynamic baroreflex response to spontaneous fluctuations in arterial pressure in conscious SHRs, as well as in the Wistar-Kyoto (WKY), the Dahl salt-sensitive, the Dahl salt-resistant, and the Sprague-Dawley rat. Observations revealed the existence of long intermittent periods (lasting up to several minutes) of engagement and disengagement of baroreflex control of heart rate.

Chemerin contributes to in vivo adipogenesis in a location-specific manner.

Since chemerin's identification as an adipokine, it has been associated with a number of human diseases including diabetes and obesity. However, the basic scientific foundation for these clinical determinations is still lacking. Fibroblastic mouse 3T3 cells are unable to develop lipid droplets if chemerin is not present.

A New Function for Perivascular Adipose Tissue (PVAT): Assistance of Arterial Stress Relaxation.

In health, PVAT secretes anti-contractile factors that relax the underlying artery. PVAT's contributions to vascular function include more than production of vasoactive substances. We hypothesized that PVAT benefits the artery by assisting the function of stress (-induced) relaxation.

Effects of high-fat diet on sympathetic neurotransmission in mesenteric arteries from Dahl salt-sensitive rat.

Obesity hypertension is driven by sympathetic neurotransmission to the heart and blood vessels. We tested the hypothesis that high-fat diet (HFD)-induced hypertension is driven by sympathetic neurotransmission to mesenteric arteries (MA) in male but not female Dahl salt-sensitive (Dahl ss) rat. Rats were fed a control diet (CD; 10 kcal% from fat) or HFD (60 kcal% from fat) beginning at 3 weeks (wk) of age; measurements were made at 10-, 17- and 24-wk.

Different blood pressure responses in hypertensive rats following chemerin mRNA inhibition in dietary high fat compared to dietary high-salt conditions.

Chemerin is a contractile adipokine, produced in liver and fat, and removal of the protein by antisense oligonucleotides (ASO) lowers blood pressure in the normal Sprague Dawley rat. In humans, chemerin is positively associated with blood pressure and obesity so we hypothesized that in a model of hypertension derived from high-fat (HF) feeding, the chemerin ASO would reduce blood pressure more than a high-salt (HS) model. Male Dahl S rats were given a HF (60% kcal fat; age 3-24 wk) or HS diet (4% salt; age 20-24 wk to match age and blood pressure of HF animals).