Hypertensive Rabbits Research Articles

Relationship of sodium retention and induction of hypertensive arterial necrosis in rabbits.

AbstractDuring the first 15 days of one-kidney, one-wrapped (1K1W) hypertension in rabbits, retention of sodium occurred compared with essentially normotensive 2K1W control rabbits (1K1W, 30 ± 9 meq/15 days vs 2K1W, −6 ± 15 meq/15 days, P < 0.02). Most of the sodium retention occurred between the fifth and eighth days of the hypertensive period (3.7 ± 0.9 meq/day vs control period, 0.8 ± 0.9 meq/day, P < 0.02). Sodium retention occurred even though sodium intakes were reduced (hypertensive period, 8.7 ± 1.0 meq/day vs control period, 16.3 ± 0.9 meq/day, P < 0.001), serum sodium and potassium levels remained normal, and no potassium retention occurred. Positive sodium balances of individual 1K1W rabbits for the first 8 days of the hypertensive period correlated directly with the degree of arterial necrosis and with the degree of cardiac enlargement (P < 0.05). Change in voluntary dietary sodium intake for the entire hypertensive period correlated directly with the elevation in blood pressure (δBP vs δNa in...

Influence of forebrain periventricular lesions on the development of renal hypertension in rabbits.

Ablation of tissue surrounding the anteroventral third cerebral ventricle (AV3V) has been demonstrated to prevent and reverse renal hypertension in the rat. The contribution of this brain area to the maintenance of hypertension in other species has not been examined. In the present investigation, an attempt was made to produce two-kidney, one clip renal hypertension in rabbits with histologically and functionally defined AV3V destruction. Electrolytic lesion of the AV3V in rabbits produced effects closely resembling those previously seen in rats: increased plasma volume and plasma sodium, temporary adipsia, no change in resting arterial pressure or heart rate, and significant attenuation of pressor responsiveness to angiotensin II (AII) delivered intracranially. However, the increase in arterial pressure observed over a 4-week period following the application of a 0.5 mm silver clip to the left renal artery (opposite kidney intact) was identical in 12 AV3V-lesioned and 12 sham-operated rabbits. Hypertension development was not accompanied by significant sodium retention, water retention, or plasma/extracellular fluid volume expansion in either group of rabbits. Pressor responses to intravenous infusions of AII and norepinephrine were identical in sham and AV3V-X rabbits. Thus, destruction of the AV3V, and the attendant reduction in the central pressor action of AII, does not alter the pattern of development of two-kidney, one clip renal hypertension in the rabbit. The contrasting results in rats and rabbits could be explained by the differing contribution of the area postrema to the pressor action of AII in the two species.

Constriction of ear arteries from normotensive and renal hypertensive rabbits against different transmural pressures.

Isolated segments of rabbit ear arteries were made to constrict against normotensive and hypertensive transmural pressures by perfusion with submaximal concentrations of norepinephrine (NE). Changes in load (force/unit length of artery) and stress (force/wall cross-sectional area) during constriction against a constant pressure have been evaluated. Weak concentrations of NE constricted the arteries equally well against transmural pressures of 80 and 120 mm Hg and, in doing so, utilized much of the contractile capacity of the muscle. A stretch-mediated, co-operative interaction between muscle cells has been put forward to explain these observations. Ear arteries from renal hypertensive rabbits differed from those of normotensive rabbits in having a higher NE threshold concentration and in constricting better against 140 mm Hg. They did so because of the mechanical advantage provided by a smaller internal radius and a thicker wall which reduced the load and stress placed on the muscle by the pressure. No muscle hyperplasia or hypertrophy was detected.

Role of bradykinin potentiation in the antihypertensive effect of captopril in conscious rabbits with two-kidney, one-clip hypertension.

The role of bradykinin potentiation in the antihypertensive effect of captopril was assessed in conscious rabbits with two-kidney, one-clip hypertension. On the 35th day after clipping the renal artery, a bolus injection of bradykinin 0.2 microgram/kg was repeated at 15-min intervals three times before and for 180 min after the administration of captopril 0.5 mg/kg. The magnitude and duration of captopril-induced hypotension were more marked in hypertensive rabbits than in controls. The bradykinin-induced hypotension was markedly enhanced by captopril. However, the bradykinin potentiation by captopril was not correlated with its vasodepressive effect. On the other hand, a close relationship (r = 0.825, p less than 0.001) was observed between plasma renin activity and the maximum reduction in blood pressure induced by captopril. The experiment performed after sodium depletion for 7 days revealed that the bradykinin potentiating effect of captopril was not affected by sodium depletion. Therefore, it is concluded that the vasodepression by captopril does not necessarily depend on its bradykinin potentiating action and the latter is not influenced by the renin-angiotensin system or fluid volume depletion.

Studies on the mechanism of mineralocorticoid-induced hypertension: evidence for the presence of an In-Situ mechanism in the arterial wall for a direct action of mineralocorticoids

Data from clinical and experimental studies indicate that mechanism(s) for action of mineralocorticoids. other than renal. must be involved in the overall effect of mineralocorticoids on circulation — increased peripheral resistance and hypertension. We have postulated existence of such a mechanism in the arterial wall and have looked for the evidence of its presence. We have found high affinity, specific binders for mineralocorticoids, and glucocorticoids. with characteristics of steroid receptors, in rabbit and lamb arterial homogenate cytosol. Moreover, these binders were found to possess also other fundamental properties of cytoplasmic steroid receptors: they translocate to cell nuclei (as steroid-receptor complexes) and bind to relatively specific “acceptor-sites” on nuclear chromatin. The mineralocorticoid with the highest affinity for the arterial mineralocorticoid receptor is 11-desoxycorticosterone (DOC); however, the possibility of a parallel existence of a specific aldosterone receptor is not ruled out. Cytoplasmic mineralocorticoid receptors are not present in veins. The steroid with the highest affinity for the arterial glucocorticoid receptor is dexamethasone. similarly as in other target tissues to glucocorticoids. A highly specific transcortinlike cortisol binder was also found in aorta cytosol. In parallel with this binder a true cortisol-receptor (translocating to cell nuclei and binding to nuclear chromatin) was also found. This points to heterogeneity of cytoplasmic glucocorticoid receptors. Furthermore, we have studied the effect of chronic administration of DOC acetate (DOCA) on intracellular sodium concentration [Na i .] and on the rate of passive Na + -influx into the cells of aorta. Both were found to be significantly higher in DOCA-induced hypertensive rabbits than in normotensive control animals. This indicates that cell-membrane permeability to electrolytes is increased as a result of chronic elevation of circulating levels of DOC, and is in accord with the findings of other investigators in other animal species. We postulate that this effect of DOC is elicited through the receptor-mediated mechanism for action of mineralocorticoids in the arterial wall; and that increased [Na i ] in arterial and arteriolar smooth muscles leads to their increased contractility, hyperresponsiveness to vasoconstrictive stimuli, hypertrophy, increased peripheral resistance, and hypertension.

Systemic and regional haemodynamic responses to isoprenaline in conscious renal hypertensive rabbits.

1. Using the electromagnetic flow probe and the radioactive microsphere technique, systemic and regional haemodynamic variables were measured in conscious normotensive and hypertensive rabbits. The rabbits were made hypertensive by unilateral nephrectomy combined with cellophane-wrapping of the remaining kidney and systemic and regional haemodynamic effects of isoprenaline infusions (0.5 micrograms.kg-1 .min-1) were compared in the two groups of animals. 2. Isoprenaline evoked increases in heart rate and cardiac index while the total peripheral resistance decreased. In the hypertensive rabbits the effects were similar, except for a significantly more pronounced decrease in blood pressure. 3. Isoprenaline increased the fraction of the cardiac output delivered to the heart, skin and fat, at the expense of the fractions to the brain, stomach, small intestine, pancreas, liver and kidney(s) in both normotensive and hypertensive animals. Local peripheral resistance was decreased, most prominently, in the heart, skin, skeletal muscle and fat. 4. In the normotensive rabbits pretreatment with propranolol (4 mg.kg-1 infused in 1 h) effectively blocked the cardiovascular responses following isoprenaline infusion. 4. Since the systemic and regional haemodynamic effects of isoprenaline were not less (if anything, slightly more) in the hypertensive than in the normotensive rabbits, our results provide no evidence for subsensitivity of beta-adrenoceptors as a contributory factor in the development of hypertension in this model.

Alkyl ether analogs of phosphatidylcholine are orally active in hypertensive rabbits.

1-0-alkyl ethers of phosphatidylcholine having an acetoyl in the second position were derived from fresh renal tissue. The main ether so derived had a 16:0 chain. The C16:0 alkyl ether was synthesized de novo. The renally derived and the synthetic ether exerted a similar and powerful antihypertensive action in hypertensive rabbits when given orally in divided doses. This action was prolonged, requiring more than 60 hours after the last input of the compound for recovery of the arterial pressure. As these ethers exerted their antihypertensive action, there was no evidence of adverse effects. Noteworthy was the failure of these depressor compounds to cause renin release. Diuresis-kaliuresis did not occur. A suggestion of sodium retention was noted.

Absence of an antihypertensive effect of 12 hour infusions of an angiotensin antagonist in chronic renal hypertensive rabbits.

The effect of a continuous 12-hour infusion of a saline solution of the angiotensin II antagonist, [Sar1, Ile8] angiotensin II, on mean arterial pressure was studied in 11 conscious New Zealand white rabbits with hypertension induced by renal artery stenosis and contralateral nephrectomy, and in 11 normotensive control rabbits. Also, the effect on mean arterial pressure of infusing saline alone for 12 hours was examined in 4 hypertensive rabbits and in 8 normotensive controls. There were no significant differences in the changes in mean arterial pressure among the 4 groups of rabbits at any hourly period during these infusions. These studies were unable to provide evidence that angiotensin II is involved in maintaining the elevated arterial pressure in this hypertensive animal model.

HYPERTENSIVE MECHANISM IN CHRONIC GOLDBLATT HYPERTENSION IN RABBITS

Sodium balance studies were performed in chronic Goldblatt type renovascular hypertensive rabbits in order to clarify the mechanism for maintaining the chronic hypertensive states in renovascular hypertension. In two kidney renovascular hypertension, the blood pressure was correlated positively with plasma renin activity and negatively with serum K and faecal Na excretion. Significant correlations were also demonstrated between the latter 3 parameters each other. On the other hand, there was no obvious relationship between the blood pressure and the above parameters in one kidney renovascular hypertension. When the clipped kidney was removed in two kidney type rabbits, a significant fall of blood pressure and significant decreases in hematocrit and Na retention were observed. The fall of blood pressure following the removal of the clipped kidney correlated significantly with the decrease in plasma renin activity, the decrease in hematocrit, the increase in serum K and the increase in faecal Na excretion.The above observations were interpreted as suggesting a possibility that the increase in plasma renin activity might play an important role in maintaining hypertension in two kidney renovascular hypertension, especially in those with marked elevation of the blood pressure. However, the evidences were not obtained that either renin-angiotensin system or one kidney renovascular hypertension.

Cardiac beta adrenoceptors and adenylate cyclase in normotensive and renal hypertensive rabbits during changes in autonomic activity.

The effects of hypertrophy and alterations in cardiac autonomic activity on left ventricular (LV) beta adrenoceptors and adenylate cyclase were measured in rabbits. Normotensive and renal hypertensive animals were exposed to three levels of chronic sympathetic activity: (i) "normal" activity; (ii) reduced activity after 2 weeks treatment with guanethidine; (iii) 2 weeks increased sympathetic activity following sino-aortic denervation. In hypertensive animals with "normal" activity LV beta receptor sarcolemma concentration was reduced by 36+ compared with the normotensive subgroup whilst total LV receptor numbers were unaltered. Isoprenaline activated adenylate cyclase was similarly affected whilst other sarcolemma marker enzymes were unaffected. Chronic guanethidine administration to normotensive rabbits increased beta receptor concentration (16%, P less than 0.05), basal and isoprenaline activated meters were unaffected. Sino-aortic denervation did not significantly affect beta receptor concentration in either group. The small changes in beta receptor concentration during alterations in sympathetic activity suggest that only a small proportion of LV beta receptors appear to be innervated. The reduction in sarcolemma beta receptor concentration in hypertensive animals appears to be a specific effect due to hypertrophy of the cardiocyte.

SYSTEMIC AND REGIONAL HAEMODYNAMICS IN EXPERIMENTAL RENAL HYPERTENSION IN CONSCIOUS RABBITS

1. The radioactive microsphere method was used to measure the distribution of cardiac output, regional flows and resistances in conscious normotensive and hypertensive rabbits implanted with an electromagnetic flow probe on the ascending aorta or pulmonary artery. Hypertension was induced by wrapping one kidney with cellophane and removing the other, and studies were performed about 5 weeks later. 2. Heart rate, stroke volume, cardiac output and total renal mass were reduced in the hypertensive animals, while the weight of, and the cardiac output distribution to left ventricle and the remaining kidney were increased. 3. In renal hypertensive rabbits, the weight normalized regional blood flow was diminished in a number of tissues, including the kidney, and, except for some organs in the splanchnic area (stomach, small intestine, mesentery and pancreas) and the fat, there was a rather uniform increase in tissue vascular resistance.

Cyclic nucleotide changes in aortic segments derived from hypertensive rabbits

Mean blood pressure increase was produced by : (1) renal constriction polus contralateral nephrectomy, and (2) cadmium acetate ingestion. Blood pressure was measured directly via the middle ear artery. Cyclic nucleotide levels were determiend by 125I-radioimmunoassay. Levels of cAMP were reduced in both hypertensive subgroups when compared to controls. The altered cAMP levels suggest a relationship of this nucleotide to the maintenance of increased blood pressure.

Carotid sinus baroreceptor reflex control of the circulation in medial sclerotic and renal hypertensive rabbits and its modification by the aortic baroreceptors.

We studied the reflex control of blood pressure, heart rate, and hindlimb vascular resistance by the carotid sinus baroreceptors in normal (N), experimental renal hypertensive (RH, one kidney renal wrap model), and medial sclerotic (MS) rabbits under urethane anaesthesia using an isolated perfused carotid sinus preparation and auto-perfused hindlimb. The contralateral carotid sinus was denervated. Compared to N rabbits, the blood pressure and hindlimb vascular resistance of RH and MS rabbits were significantly elevated at all carotid sinus pressures 15 weeks after inducing the disease process. The maximum gains of the curves relating carotid sinus pressure to vascular resistance were significantly elevated in the MS and RH rabbits, but those relating carotid sinus pressure to heart rate were significantly reduced. The changes were greatest in the RH group in which the responses also were set to a higher carotid sinus pressure. In the three groups, division of the aortic nerves produced different changes in the sigmoid curves relating carotid sinus pressure to heart rate, blood pressure, and vascular resistance. There was a linear relationship between blood pressure and basal vascular resistance (correlation coefficient 0.88).

Renal pressure-flow relationships in severely hypertensive rabbits.

AbstractThe relationship between renal perfusion pressure and renal blood flow (RBF) was studied in the contralateral or not-clipped kidneys of seven two-kidney one-clip renovascular severely hyper...

Route and rate of hydrallazine administration as determinants to its hypotensive effect in rabbits.

1. The cardiovascular responses to varying doses of hydrallazine were studied in renal hypertensive rabbits. 2. The depressor effect of hydrallazine was independent of the rate of its i.v. administration (bolus v. a 15 min constant infusion). 3. Intraperitoneally administered hydrallazine was significantly less active than equimolar i.v. doses, and the relative potency (i.p. v. i.v.) did not increase with increasing doses. 4. In spite of inferential evidence to the contrary, we did not find any pharmacodynamic support for non-linear processes being involved in metabolism of hydrallazine.

Reversal of clonidine-induced hypotension by β-adrenoceptor blocking drugs

The interaction between clonidine, propranolol and sotalol was investigated using conscious normotensive and spontenously hypertensive rabbits as well as conscious normotensive and spontaneously hypertensive rats. Clonidine (20 μg/kg) administration into the marginal ear vein of rabbits produced persistent hypotension and bradycardia. In propranolol (0.5 mg/kg, i.v.)-pretreated animals, clonidine-induced hypotension was prevented. In rats, daily oral or subcutaneous clonidine as well as propranolol produced hypotension and bradycardia. Significant antagonism of the observed hypotensive effects resulted when clonidine was given to propranolol pretreated animals or when propranolol was added to the treatment regimen of animals being maintained on clonidine. No antagonism between sotalol and clonidine was demostrable. In view of the known central site of action of clonidine, and the failure of sotalol to antagonize clonidine-induced hypotension it would appear that the central nervous system is possible site of the observed drug interaction.

Fat induced hypertension in rabbits. Effects of dietary fibre on blood pressure and blood lipid concentration

Rabbits were fed diets containing 200 g.kg-1 coconut oil, palm oil, or safflower oil. Some of the diets also contained 200 g.kg-1 cellulose. The blood pressure was measured daily by a non-invasive technique for the 2 month duration of the experiment. Blood samples were drawn after an overnight fast at intervals during the experiment and analysed for lipids. Blood pressure was always increased by a fat-enriched diet. This effect was diminished and delayed by adding cellulose to the diets, though cellulose itself had no effect on the blood pressure in the absence of fat. There was a modest negative correlation between fasting serum triglyceride concentration and the blood pressure in animals fed fat enriched diets without added cellulose, but not in animals fed diets containing both fat and cellulose. These results coupled with those of Wright, Burstyn and Gibney may serve partly to explain the observation that vegetarians have lower blood pressures than omnivores, the latter consuming diets which are relatively richer in fats and poorer in fibre than the former.

Transient and persistent changes in rabbit blood vessels associated with maintained elevation in arterial pressure.

Arteries and veins of hypertensive rabbits were examined 8 weeks after partially constricting the abdominal aorta above both kidneys, and compared with those from sham-operated animals. Structural and functional changes in blood vessels after 2 weeks, when the arterial pressure first attained a new elevated level, have been described previously, and are now compared with changes 6 weeks later. The increase in blood vessel mass could be correlated with an increase in deoxyribonucleic acid (DNA) content. In contrast to the status at 2 weeks postoperatively, there was no increased uptake of 3H-thymidine, 3H-proline, or 3H-lysine at 2 months. Furthermore, at this time cell nuclei labeled with 3H-thymidine were infrequent. Some vessels showed evidence of change in the physical characteristics of their wall. Only minimal changes were observed in those parameters of adrenergic nerve function measured -- neuronal 3H-norepinephrine uptake and vessel wall catecholamine content -- that had been markedly changed at 2 weeks. The results of this work, together with those of other studies of this model, suggest two phases of response of the arterial wall to pressure rise: an initial dynamic proliferative cellular response mainly of vascular smooth muscle associated with changes in adrenergic neuronal parameters, and a subsequent equilibrium phase characterized by an increased number of smooth muscle cells, some changes in the extracellular components, and minimal changes in the adrenergic innervation.

Noninvasive blood pressure determination in the rabbit with a Doppler ultrasound probe.

SummaryA rapid, reproducible, noninvasive technique which allows repeated determinations of blood pressure in the rabbit is described. With the rabbit in the supine position, hind legs extended, a pediatric blood pressure cuff was placed around the upper thigh. A Doppler ultrasound probe, placed over the femoral artery, was used to determine the systolic and diastolic pressures. The average pressures obtained were 132 ± 3/65 ± 1 mm Hg (± SEM) (n = 93). These correlated well with direct intraarterial recording of the blood pressure. This technique was also used to measure the elevated pressures in hypertensive rabbits. Pressure measurements varied very little from one observer to another. Repeated determinations from the same rabbit were also relatively constant. This modified auscultatory method provides an efficient method for blood pressure determination in the rabbit over a period of time.

Comparison of the effects of nine beta-adrenergic blocking agents on intraocular pressure in rabbits.

The intraocular pressure lowering effects of nine beta-adrenergic receptor blocking agents were compared using two different models of experimental ocular hypertension in rabbits. All the nine drugs possess, to different extents, a clear pressure-lowering action after topical administration into the conjunctival sac. For potency and duration of action, the best results were obtained with timolol and sotalol. Pindolol, oxprenolol, practolol, and propranolol are also fairly potent while less impressive effects were produced by atenolol, butidrine, and metoprolol. With the exception of propranolol, all the drugs were well tolerated by the ocular tissues.