Blood pressure effect Hypertensive activity

Azizi, M., Guyene, T. T., ChateUier, G., Wargon, M., and Menard, J. (1997) Additive effects of losartan and enalapril on blood pressure and plasma active renin. Hypertension. 29, 634-640. 

Adrenergic neurone blocking activity is increased when substituents are introduced into the ortho- and para-positions of benzylguanidine (Table 3.18) active compounds include the bromo (a particularly close analogue of bretylium), chloro and trifluoromethyl derivatives (LIV, R = 2-Br, 2-Cl, 2- and 4-CFa) [140, 141, 239, 242]. The 4-trifluoromethyl derivative, which has a relaxing effect on the nictitating membrane of cats comparable in intensity and duration to bethanidine, also decreased blood pressure in hypertensive dogs [141]. Certain... 

Blood pressure effect. Fruit juice, administered intravenously hy infusion to dogs at a dose of 3 mL/minute for 100 minutes, was active. Initial effect was a decrease in hlood pressure . Oil, administered to male weanling rats at a dose of 10% of diet for 5 weeks, produced significantly higher hlood pressure than other groups. Systolic hlood pressure was found related to the dietary intakes of saturated and unsaturated fatty acids. Prenatal exposure of the rats to a maternal low-protein diet abolished the hypertensive effect of the coconut oil dieH . Butyryl cholinesterase activity. Oil was administered to rats at different doses with or without clofibrate for 15 days. The hypolipidemic action of clofibrate was not... 

Effect of coffee on blood pressure and CA065 activity rennin-angiotensin-aldoster-one system and catecholamines concentration in patients with essential hypertension. Polski Merkuriusz CA066 Lekarski 1999 7(40) 159-163. 

Propranolol inhibits the stimulation of renin production by catecholamines (mediated by receptors). It is likely that propranolol s effect is due in part to depression of the renin-angiotensin-aldosterone system. Although most effective in patients with high plasma renin activity, propranolol also reduces blood pressure in hypertensive patients with normal or even low renin activity. Beta blockers might also act on peripheral presynaptic adrenoceptors to reduce sympathetic vasoconstrictor nerve activity. 

In spite of the fact that phenol oxidase probably plays no important role in the inactivation of pressor amines in the body, it has been reported that the injection of the enzyme into hypertensive rats led to a reduction in their blood pressure (141,143)- It is difficult to assess the value of these experiments because of the nonspecific depressor effects of crude protein preparations on blood pressure. For example, Prinzmetal et al. (126) found that their tyrosinase preparations inactivated by boiling decreased the blood pressure of hypertensive patients as well as did their enzymically active preparations. 

All the clinically available (J-blockers are competitive antagonists. Nonselective [3-blockers act at both (3 and (32 receptors, whereas car-dioselective ( -antagonists primarily block 3i receptors. These drugs also differ in intrinsic sympathomimetic activity, in central nervous system (CNS) effects, and in pharmacokinetics (Figure 7.5). Although all (3-blockers lower blood pressure in hypertension, they do not induce postural hypotension because the a-adrenoceptors remain functional therefore, normal sympathetic control of the vasculature is maintained. P-blockers are also effective in treating angina, cardiac arrhythmias,... 

Cocco G, Ettlin T, Baumeler HR. The effect of amlodipine and enalapril on blood pressure and neurohumoral activation in hypertensive patients with Ribbing s disease (multiple epiphysal dystrophy). Clin Cardiol 2000 23(2) 109-14. 

The effects of NCX-4016 and aspirin on the release of thromboxane TNF-a interleukin-6 and expression and activity of tissue factor (TF) in stimulated, adherent human monocytes were recently investigated (70). These data showed that NCX-4016 inhibits thromboxane generation, cytokine release, and TF activity in human monocytes via NO-dependent mechanisms. Moreover, NCX-4016 also reduces blood pressure in hypertensive rats, not simply through the direct va-sodilatory actions of the NO released by this compound, but also through possible interference with endogenous pressor compounds (71). These properties, added to its antithrombotic effects, suggest that NCX-4016 may be a safer alternative to aspirin for use by hypertensive patients. 

P blockers, because they produce fewer undesirable effects. Several P blockers have intrinsic sympathomimetic activity (act as weak agonists at some adrenergic receptors). These drugs stimulate P2 receptors, which reduces the likelihood that rebound hypertension (sympathetic reflex to fall in blood pressure) will develop. Activated P2 receptors dilate large central arteries which provide a reservoir for blood. 

Captopril, l-[(2S)-3-mercapto-2-methyl-propionyl]-L-proline, the first orally active inhibitor of the angiotensin-converting enzyme (ACE) on the market. The positive effects of captopril and other ACE inhibitors like enalapril in hypertension and heart failure result primarily from suppression of the renin-angiotensin-aldosterone system. Captopril causes a fall in blood pressure in hypertensive patients [M. A. Ondetti et al.. Science 1977,196,441 ... 

The search for this hypothetical renal antipressor agent led to the preparation of kidney extracts (65,70,71) which lowered the blood pressure in hypertensive rats and dogs (72,77,189) and showed also some activity in several patients with essential hypertension (72). The authors themselves did not regard the results on hypertensive patients as convincing (73). The active fraction was protein-free but could be precipitated by ammonium sulfate. Parenteral administration was frequently accompanied by toxic effects (77) and the material was therefore administered orally. Even then, however, undesirable symptoms were often observed after the administration of large doses (189). There is no proof that this dialyzable, orally active material constitutes an antipressor factor of the normal kidney. It remains to be seen whether hypertension Is due to a deficiency in an essential humoral agent. 

Cromakalim. Cromakalim has along half-life (254). Cromakalim at an oral dose of 1.5 mg ia humans significantly lowers blood pressure 19/12 mm Hg (systohc/diastoHc pressure). It iacreases reaal blood flow, PRA, and heart rate. Cromakalim has bronchodilating activity that is beneficial for hypertensive asthmatic patients. Because of some undesirable effects seen ia cardiac papillary muscles of animals oa long-term treatmeat, future clinical trials are to be carried out usiag the active enantiomer, lemakalim (BRL 38227). 

---