Vasodilatory effects

Indapamide has been shown to possess diuretic and iadependent vasodilatory effects (16). It lowers the elevated blood pressure and reduces total peripheral resistance without an iacrease ia heart rate. ladapamide antagoni2es the vasocoastrictiag effects of the catecholamiaes and angiotensin II (16), a property not shared by other thia2ide-type diuretics. Tripamide is also reported to have direct vasodilatory effects (13). 

Adenosine is produced by many tissues, mainly as a byproduct of ATP breakdown. It is released from neurons, glia and other cells, possibly through the operation of the membrane transport system. Its rate of production varies with the functional state of the tissue and it may play a role as an autocrine or paracrine mediator (e.g. controlling blood flow). The uptake of adenosine is blocked by dipyridamole, which has vasodilatory effects. The effects of adenosine are mediated by a group of G protein-coupled receptors (the Gi/o-coupled Ai- and A3 receptors, and the Gs-coupled A2a-/A2B receptors). Ai receptors can mediate vasoconstriction, block of cardiac atrioventricular conduction and reduction of force of contraction, bronchoconstriction, and inhibition of neurotransmitter release. A2 receptors mediate vasodilatation and are involved in the stimulation of nociceptive afferent neurons. A3 receptors mediate the release of mediators from mast cells. Methylxanthines (e.g. caffeine) function as antagonists of Ai and A2 receptors. Adenosine itself is used to terminate supraventricular tachycardia by intravenous bolus injection. 

In randomized, controlled, clinical trials, calcium channel blockers were as effective as p-blockers at preventing ischemic symptoms. Calcium channel blockers are recommended as initial treatment in IHD when /3-blockers are contraindicated or not tolerated. In addition, CCBs may be used in combination with /3-blockers when initial treatment is unsuccessful. However, the combination of a (1-blocker with either verapamil or diltiazem should be used with extreme caution since all of these drugs decrease AV nodal conduction, increasing the risk for severe bradycardia or AV block when used together. If combination therapy is warranted, a long-acting dihydropyridine CCB is preferred. (3-Blockers will prevent reflex increases in sympathetic tone and heart rate with the use of calcium channel blockers with potent vasodilatory effects. 

A skin redness reported in experimental animals (rats, rabbits, cats and monkeys) after inhalation exposure to acrylonitrile may be due to a vasodilatory effect, rather than a direct irritant action (Ahmed and Patel 1981). Guinea pigs, which do not exhibit the cyanide-type effects of acrylonitrile poisoning (see Section 2.2.1.4), were observed to have nose and eye irritation from the acrylonitrile vapors (Dudley and Neal 1942). 

The syntheses, structures and properties of wide varieties of metal nitrosyl complexes have been well documented [4, 5, 20-23]. However, the bulk of the complexes reviewed previously are of academic interest and only a few of these metal nitrosyl complexes have been considered as biologically effective NO donors. It was observed that the metal nitrosyls with significant NO+ character are subject to attack from a variety of nucleophiles and have hypertensive properties. This could be due to the strong trans- labilizing effect of NO. In contrast, the metal nitrosyl compounds with the general formula [M(CN)5NO]n, where the NO ligand was either neutral (for M = Co) or anionic (for M = Cr) showed no vasodilatory effect [24]. 

Draw and label the axes. Plot a point at a normal Pao2 and CBF as shown. Draw a horizontal line extending to the right of this point. This demonstrates that for values > 8 kPa on the x axis, CBF remains constant. Below this point, hypoxia causes cerebral vasodilatation and CBF rises rapidly. At flow rates >100 ml.l00g 1.min 1, maximal blood flow will be attained and the curve will tail off. Remember that the vasodilatory effect of hypoxia will override any other reflexes to ensure maximal oxygenation of the brain tissue. 

A further characteristic of this principle is that, if the activity of phosphodiesterase is decreased, the concentration of cyclic GMP will increase to an extent dependent upon the extent of the decrease in activity. This characteristic has been made use of by the pharmaceutical industry. Cyclic GMP has a vasodilatory effect and this is the case for the arterioles that supply blood to the corpus cavemosum in the penis, which controls the erection of the penis. Drugs were developed (e.g. sildenafil) that inhibits cyclic GMP phosphodiesterase and hence increases the cyclic GMP level which resnlts in vasodilation of the arterioles and an increase in the snpply of blood to the spongy tissue of the corpus cavemosum, which expands resulting in erection. This dmg has been found to be effective in some patients snffering from erectile dysfunction. This can be a particular problem in diabetic patients and more elderly men (Chapter 19). 

The indole alkaloid vinpocetine (93), has a vasodilatory effect and a clinical study on patients with CNS degenerative function due to vascular deficiency, demonstrated that those who were given vinpocetine, scored significantly better for cognitive function than a placebo group. However, these results are not translated into clinical use yet. 

On the other hand, )3-adrenoblockers have a minor effect on vascular tonicity. In addition, 8-adrenoblockers prevent the vasodilatory effect of epinephrine. In organs such as the heart, which are regulated mainly by )3-adrenoreceptors, )3-adrenoblockers counteract the excitatory effect of norepinephrine. 

Coronary artery disease Due to the vasodilatory effect of dipyridamole, use with caution in patients with severe coronary artery disease (eg, unstable angina, recently sustained Ml). Chest pain may be aggravated in patients with underlying coronary artery disease who are receiving dipyridamole. For stroke or transient ischemic attack patients for whom aspirin is indicated to prevent recurrent Ml or angina pectoris, the aspirin in this product may not provide adequate treatment for the cardiac indications. 

The vasodilatory effect of Hi-receptor stimulation is mainly due to an endothelial release of nitric oxide, which is able to activate the soluble guany-late cyclase in vascular smooth muscle cells. This effect is mainly responsible for the erythema seen after injection (insect sting) of histamine. Furthermore, it is responsible, together with the increased capillary permeability, for the cardiovascular symptoms seen in anaphylactic or allergic shock. 

D. The vasodilatory effects of nifedipine are largely restricted to arteries (and consequently the afterload). It does not alter venous tone (and thus preload) significantly. 

Nicotinic acid in large doses used to treat hyperlipoproteinemia causes a cutaneous flush. The vasodilatory effect is due to... 

Renal system PGE, PGE PGI2 increase glomerular filtration through their vasodilatory effects and increase water sodium excretion. 

Labetalol is a non-selective 31-, 32- and a 1-adrenoceptor antagonist. The ol-blocking properties (which are substantially weaker than the 3-blocking activity) are largely responsible for its vasodilatory effect. Labetalol is used orally in patients with phaeochromocytoma. During... 

Noradrenaline is used to treat shock-like conditions associated with peripheral vasodilatation, e.g. sepsis, systemic inflammatory response syndrome (SIRS), neurogenic shock. The rationale of its use in sepsis and SIRS is to counteract the vasodilatory effects of nitric oxide. Following the surgical removal of phaeochromocytoma and similar tumours, noradrenaline is often given to maintain blood pressure in the initial period. During and after cardiac surgery, it may be used to optimise haemodynamic parameters in combination with other drugs, such as phosphodi-esterase inhibitors. Dose... 

Labdane type diterpenes obviously exhibit a wide spectrum of actions. Primarily forskolin exhibits (a) antihypertensive properties, lowering blood pressure in different animal species through a vasodilatory effect (b) positive inotropic effects in cardiac muscle and (c) bronchodilatory effects [155] and (d) pressure-lowering properties [244]. 

Since nicotinic acid can cause unpleasant flushing and other symptoms of vasodilatation, attempts have been made to develop modified-release formulations. Modified-released nicotinic acid formulations may be better tolerated than the immediate-release formulation, because they reduce the vasodilatory effects of the drug. However, the low frequency of flushing produced by modified-release formulations may be offset by an increased risk of hepatotoxicity. Some reports have suggested a higher frequency of hepatic dysfunction with traditional modified-release nicotinic acid formulations compared with immediate-release products (2, 40). 

N-acetylcysteine has the potential to reduce the nephrotoxicity of CM through antioxidant and vasodilatory effects (66),... 

Cilostazol is a phosphodiesterase inhibitor that reduces platelet aggregation, vascular smooth muscle proliferation and also has vasodilatory effects. Earlier studies comparing cilostazol and aspirin to ticlodipine and aspirin identified no significant increase in the subacute stent thrombosis rate (21-23). Indeed, the latter has been supported by comparison of this combination to clopidogrel and aspirin (24). Two recent trials, however, have demonstrated that a much higher proportion of patients develop subacute stent thrombosis when taking cilostazol as compared with ticlodipine (25,26). The data from these trials are summarized in Table I. 

All spin traps exerted a potent vasodilatory effect upon coronary flow rate in the isolated perfused rat heart. These effects always preceded their depressive effect upon rate pressure product and were unrelated to any increase in the osmotic pressure of the perfusate. Their vasoactive potency was as follows MNP-OH >... 

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