Renally hypertensive dog

Tolerance study in conscious renal hypertensive dogs... 

Other evidence which has been adduced to support the significance of neurogenic factors in renal hypertension is the observation that the arterial pressures of normal and renal hypertensive dogs and rabbits were reduced to essentially the same level after complete destruction of the central nervous system (18,19). However, interpretation of the results obtained with this drastic procedure is difficult. Other workers have observed a sharp fall in pressure when the spinal cord was destroyed below C5 (the level of the fifth cervical vertebra) in renal hypertensive dogs, but the pressures returned to hypertensive levels as the acute effects of the operation wore off (32). Other experiments involving elimination of the central connections of the sympathetics by cervical cord section in the region of C7... 

In vivo, lacidipine -when administered orally - was found to be an effective and potent antihypertensive agent in different animal models, including SHR (ED25 = 0.5 mg kg-1, per os) and renally hypertensive dogs (ED25 = 0.004 mg kg-1, i.v.) with a sustained duration of action [11,12]. Lacidipine was also found to possess coronary and cerebral vasodilatory activity [13]. 

Huang XH, Qiu FR, Xie HT, Li J. 2005. Pharmacokinetic and pharmacodynamic interaction between irbesartan and hydrochlorothiazide in renal hypertensive dogs. J Cardiovasc Pharmacol 46 863-869. 

It lowers blood pressure in renal hypertensive dogs at 25 mg/kg/day with little change in heart rate." ... 

Experimental results relating to the hypotensive activity of 3 Hiethoxy-V-[4-(4-phenyl-1-piperazlnyl )butoxy ] acetophenone (XIV) as the monohydrochloride (Su-l4542) or dihydrochloride (Su-13396) in normotensive and renal hypertensive dogs have been reported. These were interpreted as indicating that Su-i4542 does not act by ganglionic blockade but does possess... 

In a series of 33 aralkylhutenylamines, conQ)ound XIII provided the best hypotensive activity 50 mg/kg, orally, in renal-hypertensive dogs.21... 

SKP-III97 (XXIIl) produces its antihyperteasive effects by reducing peripheral resistance via direct vasodilatation. At 5-10 mg/kg, i.v., SKF-UI97 produced hypotension and tacd ardia in anesthetized dogs and cats, and in unanesthetized, normotensive and renal-hypertensive dogs.39... 

Since the hypotensive properties of amiquinsin hydrochloride are established, the isomeric salt 22 was prepared and tested. It is hypotensive in anesthetized normotensive dogs, and it produced an antihypertensive effect in unanesthetized renal hypertensive dogs which is, however, of shorter duration than the effect of amiquinsin hydrochloride. ... 

The hydroxamlc acid XVIII lowered blood pressure and heart rate in renal hypertensive dogs and anesthetized cats. In spinal cats it showed only a pressor action. 

The benzoquinoiizine (XXIV) is a hypotensive vasodilator in anesthetized dogs and cats it lowers the blood pressure of conscious renal hypertensive dogs at 10 mg/kg/day (p.o.)The hypotensive effect of the hydrazine (XXV, L6I50) in conscious or anesthetized dogs (0.5 or 0.01 mg/kg, i.v.) appears to be due to peripheral vasodilation. The pyrazole (XXVI) is a potent vasodilator which reduces the blood pressure of cats and dogs by 40-50 mm Hg for 2 hours at 0.25 mg/kg (I.V.). It Is also active in renal hypertensive rats. ... 

An unidentified substance, named nephrin, was described by Enger (19). Nephrin is a pressor material having a prolonged action, obtained from extracts of renal cortex, but not present in any other tissues. It was also found in urine and in blood and was said to have been present in increased amounts both in hypertensive dogs and in patients with hypertension, eclampsia, nephritis, and other hypertensive conditions. Its action was not intensified by cocaine nor affected by ergotoxin and it did not act upon the guinea pig uterine muscle. As it was dialyzable, it probably was not renin. If this work is substantiated, nephrin represents yet another renal pressor substance probably of nonprotein nature. Its relation to hypertension has not been substantiated. 

Suzuki H, Ferrario CM, Speth RC, Brosnihan KB, Smeby RR, de Silva P. Alterations in plasma and cerebrospinal fluid norepinephrine and angiotensin II during the development of renal hypertension in conscious dogs. Hypertension. 1983 5 I-139-1-148. 

Spontaneously hypertensive rats can be used to screen compounds for antihypertensive effects and for effects on heart rate. The animals are dosed for one or a few days. Blood pressure and heart rate are measured by means of an inflatable cuff around the tail. Most classes of antihypertensives will be detected. Agents such as beta-adrenergic antagonists will be detected by decreased heart rate. Other rat models include deoxycorticosterone acetate (DOCA)-induced hypertensive, renal hypertensive (one or both renal arteries clamped), and stroke-prone spontaneously hypertensive rats. Hypertensive dogs produced by clamping one or both renal arteries may also be used to test or verify antihypertensive activity in a second species. 

Cls-cinnamyl guanidine an orally active hypotensi unanesthetized normotensiv hypertensive dogs. Onset also reduced the blood pre bits. The pressor effects were enhanced, whereas tho Daily oral administration thetized renal hypertensiv... 

Along with the clinical results there was good evidence from the experimental side as well. We gave guanethidine, as had Maxwell, to dogs with chronic experimental renal hypertension and showed that severe falls in blood pressure could be achieved. Yet most would agree that this form of hypertension has as its chief component a renal mechanism. Clearly it has a neural one as well. 

By analogy with the calcium antagonist nisoldipine (141), Si-methyl-silanisoldipine (24b) was found to inhibit the contractility of vascular smooth muscle52. The in vitro spasmolytic potency (Ba++-stimulated guinea-pig ileum), the antihypertensive activity (reduction in the blood pressure of the renal-hypertensive rat after peroral administration) and the cardiovascular effect (increase in the coronary sinus oxygen content in the dog after intravenous administration) of the silicon compound 24b is comparable to that of nisoldipine (141). 

Ko et al. explored how phthalides 20 and 22 mediate the translation from vasodilatation to anti-hypertensive potential. While phthalides 20 and 22 had no effect on the blood pressure of normotensive anesthetized [302] and conscious animals [303], 20 reduced both systolic and diastolic blood pressure in renal hypertensive anesthetized rats [302]. Phthalide 20 also lowered coronary arterial pressure without affecting mean arterial blood pressure in anesthetized dogs [302]. 

Ganglion blockers - At 10 mg/kg, derivatives of A-azahomoadamantane (Vll) and (VIII) lower the blood pressure of anesthetized dogs by at least 15 for two hours or more, apparently by ganglion blockade.The monomethoxymecamyI amines (IX, R, R, or R CH3O) are about as active as mecamylamine in lowering the blood pressure of renal hypertensive rats, the corresponding hydroxy derivatives are less active. 

Other Antihypertensive Agents - 7-Azaindole-5-acetamidox-ime (VIII) and indole-l-acetamidoxime (IX) exhibited antihypertensive properties in the renal hypertensive rat and dog. The EDso values for reduction of blood pressure to normotensive levels following oral administration to hypertensive rats were lk,2 t. l and l8.2 4.5 mg/kg for VIII and IX respectively. 

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