Hypertension, arterial nitric oxide

Brosnihan KB, Li P, Ferrario CM. An-giotensin-(l-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension 1996 27[part 2] 523—528. 

Increased intrahepatic resistance to portal flow increases pressure on the entire splanchnic bed an enlarged spleen (splenomegaly) is a common finding in cirrhotic patient and can result in thrombocytopenia due to splenic sequestration of the platelets. Portal hypertension mediates systemic and splanchnic arterial vasodilation through production of nitric oxide and other vasodilators in an attempt to counteract the increased pressure gradient. Nitric oxide causes a fall in systemic arterial pressure unfortunately, this activates both the renin-angiotensin-aldosterone and sympathetic nervous systems and... 

E. Stankevicius, A.C. Martinez, M.J. Mulvany, and U. Simonsen, Blunted acetylcholine relaxation and nitric oxide release in arteries from renal hypertensive rats. J. Hypertens. 20,1571-1579 (2002). 

Matoba N, Usni H, Fnjita H, Yoshikawa M. (1999) A novel anti-hypertensive peptide derived from ovalbnmin induces nitric oxide-mediated vasorelaxation in an isolated SHR mesenteric artery. FEBS Fett 452 181-184. 

Sodium nitroprusside (SNP) is both a venous and an arterial vasodilator. An important part of its vasodilator action is caused by the release of nitric oxide (NO), similarly as for the organic nitrates. SNP can only be administered via the intravenous route. It is a rapidly and short acting vasodilator. It has been used in the treatment of hypertensive emergencies and in the management of myocardial ischaemia. In spite of its vasodilator action it hardly influences heart rate, in contrast to hydralazine and minoxidil. The dosage of SNP should not be higher than 3 pg/kg/min within 48 h, in order to avoid the rise of cyanide ions and thiocyanate in the blood. 

Sodium nitroprusside is a powerful parenterally administered vasodilator that is used in treating hypertensive emergencies as well as severe heart failure. Nitroprusside dilates both arterial and venous vessels, resulting in reduced peripheral vascular resistance and venous return. The action occurs as a result of activation of guanylyl cyclase, either via release of nitric oxide or by direct stimulation of the enzyme. The result is increased intracellular cGMP, which relaxes vascular smooth muscle (Figure 12-2). 

There has been a sequential comparison of inhaled nitric oxide 40 ppm with aerosolized iloprost 14— 17 micrograms in 35 adults with primary pulmonary hypertension (125). Five of the patients had minor headache and facial flushing during inhalation of iloprost, but these symptoms were short-lived and abated a few minutes after the inhalation ended. One patient had mild jaw pain after aerosolized iloprost, but again this was shortlived. There was an unexpected increase in pulmonary artery pressure in 10 patients and vascular resistance in six patients who received nitric oxide. The authors were uncertain of the cause of this increase, as nitric oxide generally behaves as a vasodilator, but they noted that... 

Nitric oxide also produces vasodilation in vascular smooth muscle. As indicated earlier, hypertension may be perpetuated by a defect in the production of nitric oxide by the vascular endothelium. In follows that providing nitric oxide directly or administering precursors for nitric oxide production may help reduce vascular resistance and decrease arterial pressure in specific hypertensive syndromes.6 To date, inhaled nitric oxide has been used to treat acute pulmonary hypertension associated with respiratory distress syndrome in new-... 

CBF, Cerebral blood flow CCAo, common carotid artery occlusion cGMP, cyclic guanine monophosphate ICAM-1, intercellular adhesion molecule-1 ICAo, internal carotid artery occlusion MCAo, middle cerebral artery occlusion NAA, A-acetyl-aspartate NOS, nitric oxide synthase SD, Sprague-Dawley SH, spontaneously hypertensive SOD, superoxide dismutase TUNEL, transferase dUTP nick-end labeling. 

Portal hypertension in cirrhotic patients leads to arterial vasodilation in the splanchnic circulation, owing to an increased production of nitric oxide and other vasodilatory substances. This results in a low peripheral vascular resistance and a hyperdynamic circulation, with the development of arterial hypotension. In order to compensate for this... 

While working hard to lose weight and increase physical activity, you ll also want to use the special weapons described in chapter 14. All those supplements have been shown to increase levels of nitric oxide, as I explain, a gas that keeps arteries flexible, elastic, and capable of dilation to allow for increased blood flow as needed. They all have been shown to lower blood pressure. It s the pressure of blood flow against less flexible and elastic arteries that we know as hypertension. 

A 72-year-old woman, who underwent emergency resection of a giant left atrial myxoma, had pulmonary hypertension (pulmonary artery pressure 40 mmHg) and a low cardiac output (2.21/minute). Inhaled nitric oxide, 40 ppm, before cardiopulmonary bjrpass resulted in pulmonary vasodilatation and a fall in pulmonary artery pressure from 39 to 31 mmHg. This was accompanied by a fall in cardiac output from 2.4 to 1.5 1/minute and a fall in mixed venous oxygen saturation. After bypass, inhaled nitric oxide improved pulmonary and systemic hemodynamics and resulted in a rise in cardiac output from 3.0 to 3.5 l/minute. 

In a retrospective case-control study, 12 children with severe pulmonary hypertension were treated with inhaled nitric oxide followed by prostacyclin 10 ng/kg/minute for 24 hours before gradual withdrawal of nitric oxide the 12 matched controls did not receive prostacyclin (27). Only one of the patients developed rebound hypertension, indicated by arterial desaturation (a 5% or greater fall in Sa02 within 4 hours of withdrawal), while eight of 12 controls developed the rebound effect. 

Nitric oxide is produced in the endothelium, relaxes the vascular epithelium, and is a very potent vasodilator. The nitric oxide system is an important regulator of arterial BP. Hypertensive patients may have... 

FIGURE 8.6 Targets for current therapies in pulmonary arterial hypertension (PAH) and their three major pathways endothelin, nitric oxide, and prostacyclin. (From Ref. 83, with permission.)... 

Sodium nitroprusside is used for the short-term control of severe hypertension and can improve cardiac function in patients with left ventricular failure see Chapter 34). Nitroprusside acts by releasing nitric oxide (NO). NO activates the guanylyl cyclase-cyclic GMP-PKG pathway, leading to vasodilation. The mechanism of release of NO likely involves both enzymatic and nonenzymatic pathways. Tolerance does not develop to nitroprusside. Nitroprusside dilates both arterioles and venules the hemodynamic response results from a combination of venous pooling and reduced arterial impedance. In subjects with normal left ventricular function, venous pooling affects cardiac output more than does the reduction of afterload cardiac output thus tends to fall. In patients with severely impaired left ventricular function and diastolic ventricular distention, the reduction of arterial impedance leads to a rise in cardiac output see Chapter 33). Sodium nitroprusside is a nonselective vasodilator, and regional distribution of blood flow is little affected by the drug. In... 

Girard, G., Lehot, J.-J., Pannetier, J.-C., Filley, S., Ffrench, P., and Estanove, S. (1992). Inhaled nitric oxide after mitral valve replacement in patients with chronic pulmonary artery hypertension. Anesthesiology 77, 880-883. 

Weitzberg, E., Rudehill, A., Alving, K., and Lundberg, J. M. (1991). Nitric oxide inhalation selectively attenuates pulmonary hypertension and arterial hypoxia in procine endotoxin shock. Acta Physiol. Scand. 143, 451-452. 

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