The effects of short-term nifedipine treatment on responsiveness of aortic rings of cadmium-hypertensive rats.

The effects of short-term antihypertensive treatment with nifedipine on blood pressure and vascular responsiveness were studied in cadmium-hypertensive and normotensive control rats. Cadmium administration caused a significant increase in mean arterial blood pressure. Endothelin-1, noradrenaline and angiotensin II produced concentration dependent contractions of aortic rings that attained a lower maximal contraction in cadmium-hypertensive rats. Responses of aortic rings to KCl did not show a significant difference between the groups. Nifedipine administered simultaneously with cadmium inhibited the induction of hypertension. Nifedipine treatment for 5 days significantly reduced the blood pressure in cadmium-hypertensive and normotensive rats. Neither inhibition of hypertension nor normalization of blood pressure in cadmium-hypertensive rats caused an alteration in contractile responses of aortic rings to vasoconstrictors which suggested that development of decreased vascular reactivity and of hypertension occurs simultaneously in cadmium-hypertensive rats but the role of decreased vascular reactivity in maintenance of hypertension is questionable in cadmium-hypertension.

Responsiveness of aortic rings of cadmium-hypertensive rats to endothelin-1.

Cadmium administered intraperitoneally at a dose of 1 mg/kg/day for 15 days caused a significant increase in mean arterial blood pressure. Endothelin-1 and noradrenaline produced concentration-dependent contractions of aortic rings that attained a lower maximal contraction in cadmium-injected rats as compared with control rats (p < 0.05). On the other hand, responses of aortic rings to different concentrations of potassium chloride did not show a significant difference between the groups. The decreased responsiveness of the aortae of cadmium-hypertensive rats to endothelin-1 and noradrenaline could either be due to an interaction of cadmium with receptors or intracellular signal transduction pathways of these agents, or it may simply reflect the adaptive changes in vascular tissues following hypertension development.

The influence of blood pressure on intracellular Ca2+ content in erythrocytes: effects of cadmium chloride and nifedipine.

Cellular abnormalities associated with elevated Ca2+ concentrations have been postulated to be involved in the pathogenesis of hypertension. The present study was undertaken to investigate the effects of blood pressure changes on cytosolic Ca2+ levels in erythrocytes. Cadmium, which has been implicated in the etiology of hypertension was used as the hypertensive agent and the classical blocker of voltage-operated calcium channels nifedipine was used to treat hypertension. 10 weeks old male rats were divided into four groups; control, CdCl2, CdCl2 and nifedipine, nifedipine groups. CdCl2 caused elevations in blood pressure and in the cytosolic erythrocyte Ca2+ levels both of which were reduced after nifedipine administration. After nifedipine alone, cytosolic Ca2+ levels were increased. These findings suggest that cytosolic Ca2+ content decreasing action of nifedipine in the CdCl2 and nifedipine applied group could be secondary to the antihypertensive action.

Cardiovascular effects of intrathecally injected mu, delta and kappa opioid receptor agonists in rabbits.

1. Intrathecal saline, the mu opioid agonist [D-Ala2, MePhe4, Gly5-ol] enkephalin (DAGO) and delta opioid agonist [D-Pen2, D-Pen5] enkephalin (DPDPE) had no significant effects on systemic blood pressure and heart rate values. 2. The kappa opioid agonist bremazocine however, caused falls in blood pressure and reduction in heart rate. 3. Intrathecal administration of saline, DPDPE and bremazocine had no effect on baroreflex sensitivity. 4. Intrathecal administration of DAGO caused a reduction in baroreflex sensitivity; this effect was inhibited by naloxone and abolished after atenolol. 5. The role of spinal opioid systems as a possible site of action is discussed.

Morphine increases plasma immunoreactive atrial natriuretic peptide levels in humans.

Plasma immunoreactive alpha-atrial natriuretic peptide (IR alpha-ANP) levels were determined before, and at 5 and 10 min after bolus intravenous administration of morphine (0.15 or 0.30 mg/kg) in 21 otherwise healthy human subjects who underwent elective surgery. Five min after injection IR alpha-ANP levels had nearly doubled in response to both doses of morphine. At 10 min, plasma IR alpha-ANP concentrations were lower than at 5 min in the 0.15 mg/kg group suggesting that IR alpha-ANP levels peak shortly after morphine administration. Morphine has been widely used in the treatment of acute left ventricular failure and ANP is a recently discovered hormone which possesses unique favourable effects in patients with congestive heart failure when administered exogenously. The combination of these data suggests an important potential role for ANP in the mechanism of action of morphine in the treatment of acute left ventricular failure.