Vasodilators Vasopressin

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

Vasopressin is a potent vasoconstrictor that increases blood pressure and systemic vascular resistance. It may have several advantages over epinephrine. First, the metabolic acidosis that frequently accompanies cardiopulmonary arrest can blunt the vasoconstrictive effect of epinephrine this does not occur with vasopressin. Second, stimulation of P receptors by epinephrine can increase myocardial oxygen demand and complicate the postresuscitative phase of CPR. Vasopressin can also have a beneficial effect on renal blood flow in the kidney, causing vasodilation and increased water reabsorption. 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Peptides are used by most tissues for cell-to-cell communication. As noted in Chapters 6 and 21, they play important roles in the autonomic and central nervous systems. Several peptides exert important direct effects on vascular and other smooth muscles. These peptides include vasoconstrictors (angiotensin II, vasopressin, endothelins, neuropeptide Y, and urotensin) and vasodilators (bradykinin and related kinins, natriuretic peptides, vasoactive intestinal peptide, substance P, neurotensin, calcitonin gene-related peptide, and adrenomedullin). This chapter focuses on the smooth muscle actions of the peptides. 

Administration of ANP produces prompt and marked increases in sodium excretion and urine flow. Glomerular filtration rate increases, with little or no change in renal blood flow, so that the filtration fraction increases. The ANP-induced natriuresis is due to both the increase in glomerular filtration rate and a decrease in proximal tubular sodium reabsorption. ANP also inhibits the secretion of renin, aldosterone, and vasopressin these changes may also increase sodium and water excretion. Finally, ANP causes vasodilation and decreases arterial blood pressure. Suppression of ANP production or blockade of its action impairs the natriuretic response to volume expansion, and increases blood pressure. 

Conivaptan Antagonist of vasopressin (and V2) receptors Vasodilation Potential use in hypertension and heart failure hyponatremia... 

In fact, a medley of substances (autacoids), kinins, prostaglandins, leukotrienes, histamine, endorphins, serotonin, vasopressin, has been implicated. In endotoxic shock, the toxin also induces synthesis of nitric oxide, the endogenous vasodilator, in several types of cells other than the endothelial cells which are normally its main source. 

Ultimately, decompensation of the water and electrolyte balance is the result of (1.) splanchnic and peripheral arterial vasodilation, (2.) subsequent marked reduction in the effective arterial blood volume, (3.) increase in renin, aldosterone, vasopressin and noradrenaline, 4.) renal vasoconstriction with retention of sodium and water, and (5.) inadequate compensation of the plasma volume as a result of progressive hypalbuminaemia. 

Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially reduces renal medullary blood flow through the stimulation of the vasopressin Via receptor (VlaR). Studies have also shown that the vasopressin V2 receptor (V2R) may modulate AVP-mediated vasoconstriction. The transcriptional and translational sites of the VlaR and V2R in micro-dissected intrarenal vascular segments from both the cortex and medulla was studied [154]. The results indicate that VlaR mRNA and proteins are present in the isolated cortical or medullary vasculature, but the V2R mRNA and proteins were not found. This study suggests that the vasoconstrictor action of AVP within the renal medulla is mediated through the VlaR and that the modulatory V2R- mediated vasodilation is probably through the release of paracrine hormones found within the renal interstitial or tubular cells. 

Feldene piroxicam. felodipine [ban, inn, usan] (Plendil etc.) is a dihydropyridine calcium-channel blocker with VASODILATOR properties, which can be used in ANTIHYPERTENSIVE therapy and antianginal prophylaxis, felypressin [ban, inn, usan] ([Phe Lys ]vasopressin phelypressin PLV2 Octapressin Octopressin ) is a synthetic analogue of vasopressin. It is a VASOCONSTRICTOR and is incorporated into LOCAL ANAESTHETIC preparations to prolong their duration of action. (It is a constituent with prilocaine of Citanest with Octapressin .)... 

Several animal studies have demonstrated the beneficial effect of vasopressin on coronary and cerebral blood flow. Although vasopressin improves vital organ perfusion during VF, myocardial oxygen consumption is lower with vasopressin than with epinephrine. Vasopressin also may have a beneficial effect on renal blood flow by stimulating V2 receptors in the kidney, causing vasodilation and increased water reabsorption. With regard to splanchnic blood flow, however, most studies have shown that vasopressin has a detrimental effect compared with epinephrine. ... 

Landry DW, Levin HR, Gallant EM, et al. Vasopressin deficiency contributes to the vasodilation of septic shock. Circulation 1997 95 1122—... 

---