The Role Of Endothelin Receptor Populations On Ventricular Cardiomyocyte Membranes Of Spontaneous Hypertensive Rats

Table 5. The effects of Atropine measured by the ventricle of the frog’s heart by amplitude, period, and BPMs.

In the presence of excess T3 and T4, an increase in number as well as affinity of beta-adrenergic receptors in the heart is noted. These receptors facilitate the action of "fight, flight and fright" hormones ( epinephrine, norepinephrine) which are positively chronotropic ( beat faster) and inotropic ( pump harder) to the heart. This may then lead to cardiac failure in older patients.

Baroreflex failure syndrome is a rear cardiovascular disease that prevents afferent baroreceptor nerve cells from monitoring and regulation blood pressure. Baroreceptors respond to high blood pressure by increasing their firing rate, decreasing sympathetic outflow, heart rate, and contractility. This causes an increase in parasympathetic outflow from the vagus nerve, which causes vasodilation, a decrease in mean arterial pressure, and lowers blood pressure. Baroreceptors that are found within the carotid sinus and aortic arch, and travel along the glossopharyngeal and vagus nerves. They send their sensory input about blood pressure to the cardio-regulatory center of the medulla oblongata, and a sympathetic response leads norepinephrine (NE) to bind to beta-adrenergic receptors on autorhythmic cells to increase Na+ permeability through funny channels, and Ca2+ permeability through T-type channels. This triggers a faster drift, a less negative membrane potential, and increases the rate of sinoatrial (SA) node firing, and signal conductance. The exact mechanism for initiation of the disease is still unknown, but recent studies have hypothesized that the syndrome degrades neurons on both sides of the solitary tract located in the medulla, and triggers cell necrosis of the glossopharyngeal and vagus nerves. This cranial nerve damage impairs the

It should be noted that the focus of this paper will be on CHD due to atherosclerosis, which makes up over 90% of all ischaemic heart diseases [1].

(c) Estimate the EC50 values for the effects of acetylcholine and nitroprusside in both types of arterial ring, and present these in a table.

In an effort to increase cardiac output, the sympathetic nervous system is activated, through baroreceptors in the aortic arch, as an early compensatory mechanism which provides inotropic support and maintains cardiac output (Cadwallader, 2013; Yelle & Chaudhry, 2016). These compensatory mechanisms include increased heart rate, myocardial remodeling, and increased fluid volume. Chronic sympathetic activation eventually increases the stress placed on the heart and causes further weakening in cardiac function (Markaity, 2012; Yelle & Chaudhry, 2016).

Both receptors are differentiated by their selective affinity for different non-peptide ligand although they have the similar binding for angiotensin II (De Gasparo, Catt, Inagami, Wright, & Unger, 2000). Both receptors belong to the seven-transmembrane domain, G-protein coupled receptor family (Saavedra, 2005). However, AT2 receptor shares only 32-34% amino acid identity with the AT1 receptor. AT1 receptor was found in the areas related to neuroendocrine control and autonomic regulation of cardiovascular function and the limbic system (Tsutsumi & Saavedra, 1991). The physiological actions of angiotensin II in the brain, such as regulation of blood pressure, fluid balance, and hormone secretion, are mediated by the AT1 receptor. Additionally, systemic angiotensin II affects the brain functions through AT1 receptors located in the circumventricular organs which are devoid of BBB and derived angiotensin II may act at many sites in the central nervous system located behind the BBB (Unger & Scholkens, 2004). On the other hand, AT2 receptor acts a role in brain organogenesis and in the function of sensory and motor systems (Tsutsumi & Saavedra, 1991). However, the physiological functions of the AT2 receptor are still uncertain (De Gasparo & Siragy, 1999; Saavedra, 2005). Thus, the role of brain angiotensin II appears to be multiple and complex

Since the evolution of H2S as an essential gasotransmitter at cellular level, and based on the fact that H2S characteristically similar to NO; researchers aimed to investigate the physiological effects of H2S on cardiovascular system, proposing that H2S donors may become a potential treatment for various cardiovascular abnormalities including atherosclerosis, hypertension, vasoconstriction and cellular apoptosis induced by reactive oxygen species [24-26]. The cellular mechanism by which H2S induce cardiovascular effects is not well illustrated yet. A recent study suggested that H2S can reduce heart rate and blood pressure through KATP channel activation when intracerebroventricular NaHS (H2S donor) significantly reduced the blood pressure and heart rate of experimental rats, while Glibenclamide, a potent KATP channel blocker, effectively attenuated and reversed the effect of NaHS on heart rate and blood pressure [38].

The pathophysiology on cardiovascular diseases (hypertension, heart disease, and coronary artery disease) has skyrocketed since the early 1990s. The pathophysiological continuum runs hand-in-hand with the plan and with the clinical continuum. Thus meaning, that this will provide researchers with a description in the progressive process of cardiovascular diseases such as hypertension, at the molecular level or even the cellular level for these types of diseases (Demarco, Aroor, & Sowers, 2014). Cardiovascular disease also leads to endothelial dysfunction which often leads to a lot of bad health events to happen such as vascular remodeling and inflammation in the target-organ pathology. Factors like hypertension, smoking, drinking alcohol, diabetes,

ET-1 activates two subtypes of endothelin receptors (ETA and ETB receptors) which are guanine nucleotide-binding proteins(4). The two receptors have different locations within the vasculature and mediate different downstream pathways. As a result, ET-1 can have diverse effects on the vasculature.

Calcium measurements were made with a ratio imaging system (In Cyt Im2; Intracellular Imaging, Cincinnati, OH) using wavelengths of 340 and 380 nm and an emission wavelength of 505 nm. At least 5 cells were selected in each experimental condition, and experiments were repeated in at least three separate animals. The goblet cells were incubated in an inhibitor before RvD1 10-8 M or RvE1 10-9 M was added. The cholinergic agonist carbachol (CCh) (purchased from) was used as a positive control, as its pathways are known. The phospholipase C (PLC) inhibitor, U73122 (purchased from), and the control, U73343, were added 15 minutes before Rvs or CCh stimulation. 2-aminoethoxydiphenylborane (2-APB) (Tocris Biosciense, Bristol, UK) is an Inositol triphosphate (IP3) receptor antagonist. It was added 10 minutes before stimulation. The calmodulin-dependent protein kinase II inhibitor, Kn93 (purchased from), was added 30 minutes before stimulation. The control was Kn92. 1-butanol (purchased from), a phospholipase D (PLD)

“Strong vagal stimulation can decrease the strength of the heart muscle contraction by 20 to 30 percent” (Hall, 2011 p.120). In a study done on canines under anesthesia, sympathetic stimulation was inhibited when concurrent vagal activity was present and cardiovascular effects seen included heart rate reduction by inhibition of the sympathetic nervous system and by direct hyperpolarization of sinus nodal cells. Vagal parasympathetic activation was shown to predominate over sympathetic activation (Levy & Zieske, 1969). This response is known as “accentuated antagonism” (Olshansky et al. 2008). In the Contemporary Review of Cardiovascular Medicine and Parasympathetic Nervous System and Heart Failure published by Dr. Brian Olshansky and his colleagues at the University of Iowa, epidemiological data is examined that “indicates that the resting heart rate, a measure of vagus nerve function, predicts mortality” (Olshansky et

For frogs, the mean mass specific heart rate experienced higher rates when exposed to Epinephrine (df=18 t-stat=-13.28; p<0.01) (Figure 1). The frog’s contraction strength mean experienced no increase when exposed to Epinephrine (df=18 t-stat=0.11; p=0.917) (Figure 1). Under Nicotine, the frog’s

Hearts were treated with the CaM kinase inhibitor KN-93 or the inactive analog KN-92 (0.5 μM) for 10 min before clofilium exposure. Early afterdepolarizations (EADs) were largely suppressed by KN-93 compared to KN-92. There were little differences in parameters favoring EADs such as monophasic action potential duration or heart rate in KN-93- or KN-92-treated hearts. CaM kinase activity in situ increased 37% in hearts with EADs compared to hearts without EADs. This increase in CaM kinase activity was prevented by pretreatment with KN-93.

Both The sympathetic and parasympathetic nervous system innervate the blood vessel’s walls and regulate vascular smooth muscle contractility and hence tension. Endothelial Cells of large vessels are not innervated by ANS by direct means, whereas the endothelium of the the arterioles (microvasculature) receive direct contacts from ANS nerve endings(Burnstock, 1990). Nerve endings do not form synapses with vascular cells instead release neurotransmitters that can reach target cells (Hirst, Bramich, Edwards, & Klemm, 1992).