Cardiac and Kidney Weight Indices following Dietary Salt Loading and/or Chronic Nitric Oxide Synthase Inhibition in the Hooded (Aguti) Rat.

OBJECTIVES: This study was designed to investigate if dietary salt-loading and/or chronic Nitric Oxide Synthase (NOS) inhibition are associated with cardiac hypertrophy and changes in renal mass in the hooded (Aguti) rat. METHODS: Hooded rats 8-10 weeks old were divided into 4 groups viz: control, salt, L-NAME (N?-L-Arginine Methyl Ester) and salt + L-NAME. Control rats were given a normal rat diet and water. Hypertension was induced in hooded rats by giving the following treatments: rats in the salt group were given an 8% NaCl diet and water for 6 weeks; rats in the L-NAME group were fed the normal rat diet and given water containing L-NAME at a dose of 100mg/Kg/day for 4 weeks; rats in the salt + L-NAME group were given both treatments. The rats (n = 8 per group) were anaesthetized and the hearts and kidneys excised. The cardiac weight indices and the kidney weights were measured. RESULTS: The cardiac weight, cardiac weight index, left and right ventricular weight indices and kidney weight showed no significant difference in the test groups compared to control. Kidney weight/body weight (g/100g body weight) increased significantly (P<0.05) in salt+L-NAME rats (0.35 +/- 0.015) compared to control (0.31 +/- 0.013), salt-loaded (0.29 +/- 0.013) and L-NAME rats (0.20 +/- 0.010). CONCLUSIONS: Six weeks of dietary salt-loading and /or four weeks of L-NAME-loading were not associated with cardiac hypertrophy in the hooded rat. However a combination of both manoeuvres resulted in renal hypertrophy.

Role of nitric oxide in salt and water excretion in experimental hypertension in hooded (Aguti) rats.

OBJECTIVES: The present study was designed to investigate the suitability of the hooded rat in experimental hypertension studies and to investigate some mechanisms underlying the development of hypertension. METHODS: Hooded rats were randomly divided into 4 groups: control, Salt, L-NAME (N' -Nitro-L-Arginine Methyl Ester) and salt+L-NAME. Control rats received a normal rat chow. Hypertension was induced in the test groups by giving 8% salt and/or 100mg/kg/day L-NAME for 6 and/or 4 weeks respectively. Urine and serum samples were collected from the rats and analysed for their cation contents. The blood pressure of the rats was measured. RESULTS: The mean arterial pressure (mean +/- SEM; mm Hg) increased significantly in the test groups of rats (salt: 138.3+/-4.0; L-NAME: 165.7+/-6.0; salt+L-NAME: 133.35.2) when compared with control (88.42.7; P<0.05). Water consumption, urine volume and Na+ excretion increased significantly in salt-loaded and salt+L-NAME groups compared with control (P<0.05) but remained similar in L-NAME rats. These values were however significantly less in salt+L-NAME rats compared with salt loaded rats (P<0.05). Urinary K+ excretion, serum Na+ and K+ concentrations remained similar in all groups. CONCLUSIONS: These results suggest that the hooded rat may be useful for experimental hypertension studies. Attenuation of the diuretic and natriuretic responses to salt loading in the presence of L-NAME suggests that nitric oxide is involved in the mechanisms involved in these responses. It is concluded that nitric oxide deficiency may exacerbate salt and volume retention in salt-loaded rats and possibly play a role in the subtle renal defect underlying salt sensitive hypertension.

Endothelum-dependent and-independent relaxations in aortic rings obtained from hypertensive hooded (Aguti) rats.

Experimental hypertension studies are few in the hooded (Aguti) rat. The present study was designed to investigate the usefulness of this rat strain for experimental hypertension studies and to test the hypothesis that the hypertension may be associated with a diminution of endothelium dependent and independent relaxations. Hypertension was induced in inbred hooded rats (n=8 each) by administering 8% salt in the diet and /or 100 mg/kg/day Nomega-nitro-L-arginine-methyl-ester (L-NAME) in the drinking water for six and/or four weeks respectively. The rats were anaesthetized using a 25% urethane and 1% chloralose mixture given intraperitoneally at a dose of 5 mg/kg. Their blood pressure was measured invasively. Thereafter, relaxations of rat aortic preparations to acetylcholine, histamine and sodium nitroprusside (SNP) were assessed using standard organ bath conditions. Probability level of 0.05 was taken as statistically significant. The mean arterial pressure (MAP;mm Hg) rose significantly in all test groups (Salt: 148.3 +/- 4.6; L-NAME: 181.7 +/-8.3; Salt+L-NAME:154.9 +/-8.7) compared with control (94.2 +/-6.8; [P < 0.05]. The MAP was significantly [P < 0.05] higher in the L-NAME group than in all the other groups. The heart rate fell significantly in the salt + L-NAME group compared to control [P <0.05].The IC50 of acetylcholine in aortic rings from L-NAME rats (7.9 x 10(-1) +/- 6.0 x 10(-3)) was significantly higher than in rings from control (9.4 x 10(-8) +/- 2.8 x 10(-8)), salt (7.8 x 10(-7) +/- 4.7 x 10(-7)) and salt + L-NAME (3.3 x 10 (-7) +/- 2.1 x 10(-7)) rats [P < 0.05]. The IC50 of histamine and SNP in the rings from the test groups of rats showed no significant difference from control. Also, endothelium dependent and independent relaxations were preserved in the various forms of hypertension studied except in chronic NOS inhibition where the former was attenuated in response to acetylcholine.

Role of the endothelium in the vascular effects of vitamin C in rats.

The present study was undertaken to determine whether vascular responsiveness and endothelial function were altered in rats after 8 weeks of vitamin C treatment. Thoracic aortae were isolated from control and vitamin C-treated rats and analysed for changes in vascular reactivity. Vitamin C treatment attenuated the contractile response of aortic rings to noradrenaline and KCl. Removal of the endothelium increased the sensitivity of control rings but did not alter the effect of vitamin C. Endothelium-dependent relaxation to acetylcholine was significantly (P<0.05) enhanced by vitamin C, but the endothelium-independent relaxation response to sodium nitroprusside was not affected by vitamin C. The results suggest that the endothelium is not involved in the reduction in vascular sensitivity to contractile agonists caused by vitamin C. In addition, the enhancement of endothelium-dependent relaxation may be due to protection of nitric oxide against inactivation by oxygen free radicals.

Chronic administration of aqueous extract of Hibiscus sabdariffa attenuates hypertension and reverses cardiac hypertrophy in 2K-1C hypertensive rats.

The effect of aqueous extract of petals of Hibiscus sabdariffa (HS) on the established stages of 2-Kidney, 1-Clip renovascular hypertension was investigated in Sprague-Dawley rats. Renovascular hypertension was induced by subjecting the animals to left renal artery clamping using a 0.2mm silver clip under ether anesthesia. Sham-operated (Sh-Op) rats served as controls. Six weeks after renal artery clamping, one group of hypertensive rats (blood pressure (BP) >140 mmHg) received HS (250 mg/kg/day) in drinking water (2K-1C+HS). The second group (2K-1C) and the sham-operated (Sh-Op) controls, received drinking water. BP was monitored weekly using rat-tail plethysmography. After 8 weeks, 2K-1C+HS had a reduction in systolic BP (139.6+/-1.6 mmHg) compared to 2K-1C (174+/-2.4 mmHg, n=5; P<0.001). No significant difference was found in BP of 2K-1C+HS and Sh-Op (139.6+/-1.6 mmHg versus 132+/-3.4 mmHg). A reduction in heart rate in 2K-1C+HS was observed (388+/-3.7 bpm versus 444+/-6.8 bpm in 2K-1C and 416+/-9.3 in Sh-Op, n=5; P<0.001). The hearts of 2K-1C were heavier than those of 2K-1C+HS (0.74+/-0.03 g versus 0.66+/-0.03 g, n=5; P<0.05). Cardiac weight of 2K-1C+HS was comparable to those of Sh-Op (0.57+/-0.04 g). Serum creatinine and plasma electrolytes were not different from controls. This study suggests that HS exhibits antihypertensive and cardioprotective effects in vivo and supports the public belief that HS may be a useful antihypertensive agent.

Chronic ethanol consumption alters vascular smooth muscle responses in rats.

1. The effect of chronic ethanol (10%) consumption for 5 months on vascular smooth muscle (VSM) using aortic rings of both sexes of Sprague-Dawley rats was studied. 2. Chronic ethanol consumption increased the sensitivity of VSM to noradrenaline (NA) in both male and female ethanol-treated rats. 3. There was no significant difference in the contractile response of male and female ethanol-treated rats to NA. Hence, the enhancement of vascular contractility to the agonist due to chronic ethanol consumption is independent of gender. 4. Vascular relaxation induced by acetylcholine showed similar responses in all experimental groups. Thus, chronic ethanol consumption seems to have no significant effect on the production of endothelium-dependent relaxing factor. 5. However, the VSM sensitivity to potassium chloride was increased in female ethanol-treated rats, whereas male ethanol-treated rats had similar responses as controls. 6. The results suggest that the effect of chronic ethanol consumption on VSM varies with gender. Impairment of VSM in male ethanol-treated rats is due partly to changes in the receptor-operated channel, whereas in females it is due to changes in both receptor- and potential-operated channels.

Vitamin C lowers blood pressure and alters vascular responsiveness in salt-induced hypertension.

The present study was undertaken to investigate the effect of vitamin C treatment on blood pressure and vascular reactivity in salt-induced hypertension. Male Sprague-Dawley rats were fed a normal rat diet, a high-sodium (8% NaCl) diet, a normal rat diet plus vitamin C treament (100 mg x kg(-1) x day(-1)), or a high-sodium diet plus vitamin C treatment for 6 weeks. Salt loading significantly increased blood pressure, which was attenuated by vitamin C treatment. Aortic rings from the different groups were suspended for isometric-tension recording. The contractile response to noradrenaline was significantly increased in the salt-loaded rats. Vitamin C reduced the sensitivity of aortic rings to noradrenaline in rats on normal and high-sodium diets. In noradrenaline-precontracted rings, the relaxation response to acetylcholine, which was attenuated in the salt-loaded rats, was restored by vitamin C treatment. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) abolished the enhanced response to acetylcholine caused by vitamin C. The results suggest that the antihypertensive effect of vitamin C is associated with a reduction in vascular sensitivity to noradrenaline and enhancement of endothelium-dependent relaxation due to increased nitric oxide bioavailability.

Chloroquine reduces blood pressure and forearm vascular resistance and increases forearm blood flow in healthy young adults.

The effects of chloroquine on resting blood pressure, forearm blood flow (FBF), and forearm vascular resistance (FVR) and on the responses to cold stimulation were studied in healthy young adults. Chloroquine sulphate (800 mg) reduced systolic pressure and increased FBF (P < 0.05) but had no effect on resting FVR. Cold immersion increased systolic pressure (from 108.8 +/- 1.7 mmHg to 127.8 +/- 6.9 mmHg; P < 0.05) diastolic pressure (from 73.4 +/- 2.7 to 95.2 +/- 6.2 mmHg; P < 0.01) and FVR (from 5.9 +/- 0.9 to 13.0 +/- 1.9 a.u.; P < 0.001) but reduced FBF (from 14.3 +/- 1.64 to 10.1 +/- 1.29 ml min-1; P < 0.05). Chloroquine reduced the increase in FVR reduced by cold stimulation (P < 0.01), but had little effect on the BF and FBF responses to cold stimulation. The hypotensive effect of chloroquine could be attributed, at least in part, to the observed fall in vascular resistance.

A comparison of the effects of salbutamol, etilefrine and dextran during hypotension and low cardiac output states in rabbit.

The effects of salbutamol (25 and 50 micrograms/kg), etilefrine (50 and 200 micrograms/kg) and dextran (8 ml/kg) on cardiovascular function have been studied in the rabbit. The three drugs raised the resting cardiac output (with salbutamol producing delta max 52%, P less than 0.001, n = 5) and right heart filling pressure (RHFP, delta max from dextran 3.5 cmH2O; P less than 0.001, n = 6) and lowered total peripheral resistance (TPR, delta max from salbutamol 46%, P less than 0.001, n = 5). However, TPR rose with the 200 micrograms/kg etilefrine (P less than 0.05, n = 5). Pulse pressure rose with salbutamol (P less than 0.001, n = 6) and etilefrine (P less than 0.05, n = 6). Etilefrine raised resting BP (delta max, P less than 0.001, n = 6); salbutamol lowered resting BP (delta max, P less than 0.001, n = 6) while dextran (n = 6) had little effect on resting BP. The actions of salbutamol are mediated mainly through beta 2-adrenoceptors although the drug also has some minor beta 1-adrenoceptor action. With etilefrine, the increase in cardiac output and the reduction in TPR are mediated through beta-adrenoceptors while the increases in RHFP, blood pressure and TPR are a direct action on the alpha-adrenoceptors. However, during haemorrhage the fall in diastolic pressure produced by salbutamol was considerably reduced while the reduction in mean BP and systolic pressure (which sometimes rose) was abolished. Dextran raised BP during hypotension produced by either sympathectomy or haemorrhage but not during normotension. The reflex recovery in RHFP and the reflex tachycardia were slightly attenuated during lower body negative pressure (LBNP) after salbutamol or dextran. The reflex recovery in blood pressure was complete and the pressure sometimes exceeded the resting level by up to 10 mmHg during LBNP after salbutamol, etilefrine (50 micrograms/kg only) and dextran. The reduced TPR (presumably due to vasodilation) and the increases in cardiac output and RHFP at an adequately maintained blood pressure produced by suitable doses of the three drugs may be useful in the management of circulatory shock and related states.

Functional interaction between angiotensin and sympathetic reflexes in cats.

1. Lower-body negative pressure (LBNP) was used to stimulate sympathetic reflexes in anaesthetized cats. At -50 mmHg for 10 min it caused transient reduction in central venous pressure and systemic arterial blood pressure. Arterial blood pressure was then restored within 30 s and there was a tachycardia. Central venous pressure showed only partial recovery. The resting level of plasma renin activity (PRA; 2.9-3.2 ng h-1 ml-1) did not change until approximately 5 min into the manoeuvre. 2. When converting-enzyme inhibitor (CEI) was given 75 s after the onset of suction it caused a greater and more sustained fall in arterial blood pressure than when administered alone. The angiotensin II (ANG II) antagonist [Sar1,Ala8] ANG II produced similar effects after a short-lived pressor response. 3. This prolonged fall in arterial blood pressure produced by CEI was not associated with reduced sympathetic efferent nerve activity. This indicates that the inhibitor affects one of the peripheral actions of angiotensin and in so doing produces vasodilatation of neurogenic origin. 4. These findings suggest that angiotensin, at a level which does not exert a direct vasoconstrictor action, interacts with the sympathetic nervous system to maintain arterial blood pressure when homeostatic reflexes are activated. A reduction in the efficiency of these reflexes by CEI may contribute to its hypotensive effect.

Angiotensin activates sympathetic reflexes in the anaesthetized cat.

1. Lower-body subatmospheric pressure has been used to stimulate sympathetic reflexes in anaesthetized cats and the effects of an angiotensin converting enzyme inhibitor and [Sar1, Ala8]angiotensin II have been investigated on this reflex. 2. At the prevailing level of renin activity (2.9-3.2 ng of angiotensin I h-1 ml-1) the converting enzyme inhibitor had no effect on blood pressure yet it potentiated the initial fall in blood pressure caused by the reduced pressure and it impaired its recovery. After 10 min, therefore, blood pressure was still reduced after converting enzyme inhibitor treatment whereas in control experiments full recovery occurred within 30 s. 3. When converting enzyme inhibitor was given 75 s after the start of a 10 min period of reduced pressure, at a time when plasma renin activity had not been increased, it caused a greater and more sustained fall in pressure than it caused when administered alone. The angiotensin II antagonist, [Sar1,Ala8]angiotensin II, produced similar effects. 4. These findings suggest that the renin-angiotensin system interacts with the sympathetic nervous system to maintain systemic arterial pressure.

The effects of the antagonists of the renin-angiotensin system on cardiovascular response to lower-body subatmospheric pressure in the anaesthetized cat.

1. Lower-body subatmospheric (negative) pressure led to a prompt reduction in central venous pressure and arterial blood pressure. Arterial blood pressure was then restored within 30 s and there was a tachycardia. These reflex responses have been used to investigate the role angiotensin plays in blood pressure control. 2. The initial plasma renin activity (2.9 ng of angiotensin I h-1 ml-1) did not change during the brief lowering of pressure. Before pressure was lowered neither the angiotensin-converting enzyme inhibitor nor a competitive antagonist, [Sar1, Ala8]-angiotensin II, lowered arterial pressure. 3. Nevertheless, after inhibition of the renin-angiotensin system by these agents, the reduction in blood pressure induced by lower-body negative pressure became greater and the blood pressure recovery was impaired. 4. The findings suggest that angiotensin, at a blood concentration which has no direct effect on blood pressure, interacts with the sympathetic nervous system to maintain arterial blood pressure.