Isao Iyoda

Centrally-induced vasodepressor responses to diltiazem, a calcium channel blocker, in rats.

The effects of a calcium channel blocker, diltiazem, on central cardiovascular regulation were investigated by injecting it intracerebroventricularly (i.c.v.) in urethane-anaesthetized rats. The blood pressure decreased immediately after the injection returning to baseline level 20-30 min later. Both heart rate and abdominal sympathetic nerve activity decreased correspondingly. Diltiazem injected intravenously (i.v.) decreased both blood pressure and heart rate without affecting sympathetic nerve firing. Although the central pressor responses to carbachol and prostaglandin E2 were not affected by i.c.v. pretreatment with diltiazem, diltiazem attenuated the pressor responses to angiotensin II. Furthermore, electrical lesioning of the anteroventral third ventricle (AV3V) area significantly attenuated the depressor responses to diltiazem injected i.c.v. These results suggest that diltiazem injected i.c.v. affects the central nervous system to decrease sympathetic outflow, and thereby to attenuate the central vasopressor effects of angiotensin II in the brain AV3V area.

Centrally-induced vasopressor responses to ouabain are augmented in spontaneously hypertensive rats.

Dihydroxyouabain (ouabain), 1.0-10 micrograms, per rat, injected intracerebroventricularly, produced dose-related vasopressor responses accompanied by corresponding increases in abdominal sympathetic nerve activity in 16 weeks old Wistar (NT) rats anesthetized with urethane. The heart rate then also increased, dose-dependently, to ouabain injected in doses up to 10 micrograms. However, 100 micrograms produced arrhythmia resulting in bradycardia. Pressor effects were appreciable within one minute after the ouabain injection, but did not become maximal until between 7-10 min later. Either the removal of sympathetic vasomotor tone by surgical section of the spinal cord or intravenous pretreatment with a vasopressin antagonist significantly reduced the vasopressor responses in the NT rat. Ouabain, 10 micrograms, injected intraventricularly in 16 weeks old Kyoto Wistar rats produced similar cardiovascular responses to those in the NT rat, but the magnitude of the blood pressure responses, along with the heart rate and sympathetic responses, was larger in SHR than in WKY. These results suggest that dihydroxyouabain acts centrally to elevate the blood pressure by increasing not only the sympathetic discharge but also, perhaps, the secretion of vasopressin. In light of previous studies showing that SHRs exhibit both sympathetic hyperactivity and hypersecretion of vasopressin, the present results suggest that their enhanced responsiveness to ouabain could result from both the sympathetic hyperactivity and an enhanced vasopressin release as a result of the centrally injected ouabain.

Vasopressor Responses to Centrally-Administered Steroid Hormones are Mediated VIA a Renin-Angiotensin System in the Rat Brain

Centrally-induced cardiovascular effects of steroid hormones were investigated by injecting them intracerebroventricularly (i.c.v) in both conscious and urethane-anesthetized rats. Conjugated estrogens and hydrocortisone produced similar vasopressor responses accompanied by corresponding increases in the abdominal sympathetic nerve activity, which attained the peak elevation about 5 minutes following the injection. Because drinking behavior was observed following i.c.v. injections of the estrogens in conscious rats, possible involvement of a brain angiotensin mechanism was then explored; an angiotensin II (A II) antagonist with (1–Sar, 8–I1e) A II injected i.c.v. abolished both the pressor and sympathetic nerve responses to the steroids. Angiotensin I converting enzyme inhibitor, captopril, also significantly attenuated the pressor responses. Electrical lesioning of the anteroventral, third ventricle (AV3V) in the brain attenuated the pressor responses to these steroids significantly. Intravenous injectio...