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The cardiovascular effects of the 5-HT1A receptor agonists MDL 73,975 (8-[2-(2,3-dihydro-8-methoxy-1,4-benzodoxin-2-yl)methylaminol++ +]-ethyl]-8- azaspiro[4,5]decane-7,9-dione hydrochloride) and flesinoxan (10-300 micrograms/kg subcutaneously, s.c.), the 5-HT1A receptor antagonist NAN 190 (2-[4-[4-(2-methoxyphenyl)-1-piperazinyl]butyl]-1H-isoindole-1,3(2H)- dione,1,2-ethanedioate), and the alpha 1-adrenoceptor antagonist prazosin have been investigated in conscious normotensive and renal hypertensive dogs. In normotensive dogs the increases in heart rate and respiratory rate induced by both agonists were dose-related, as were the decreases in systolic and diastolic blood pressure induced by MDL 73,975. Both compounds caused a dose-related increase in the intensity of the '5-HT syndrome'. After pretreatment with NAN 190 (100 micrograms/kg s.c.) the increases in heart rate, respiratory rate and symptoms of the '5-HT syndrome' were significantly reduced but the decreases in systolic and diastolic pressure were additive. Pretreatment with prazosin (100 micrograms/kg s.c.) antagonized the '5-HT syndrome' and the increase in respiratory rate. Similar responses were evident in renal hypertensive dogs. Tolerance did not develop to the increases in heart rate, respiratory rate and manifestations of the '5-HT syndrome' in normotensive dogs during 5 days of treatment with MDL 73,975 or flesinoxan. In conclusion, MDL 73,975 and flesinoxan induced a 5-HT1A receptor-mediated fall in blood pressure but the changes in heart rate, respiratory rate and the '5-HT syndrome' are probably mediated by alpha 1-adrenoceptors.

The effects of pentobarbitone anaesthesia on the cardiovascular changes induced by centrally administered taurine have been investigated in spontaneously hypertensive (SHR) and normotensive rats. Administration of taurine (100-400 micrograms) into the lateral cerebral ventricle (i.c.v.) of anaesthetised SHR and normotensive rats induced a dose-related fall in systemic blood pressure and heart rate, which tended to be of a greater magnitude in the SHR. In anaesthetised rats attached to a ventilator, taurine was not as potent at inducing a fall in systemic blood pressure, approximately double the dose being required to produce the same cardiovascular changes as that which occurred in anaesthetised rats without a ventilator. In conscious normotensive rats taurine had no effect on blood pressure until a dose of 800 micrograms was administered i.c.v., whereas in conscious SHR, a small, but significant depressor response was evident with 400 micrograms. These findings demonstrate that pentobarbitone anaesthesia sensitises the rats to the cardiovascular effects of taurine, partially through a mechanism which involves respiratory depression. Conversely in conscious rats a much higher dose of taurine is required to induce a fall in arterial pressure and heart rate per se.

Low doses of 8-OH-DPAT (10 and 25 micrograms/kg) administered subcutaneously (s.c.) to renal hypertensive mongrel dogs caused decreases in systolic blood pressure which persisted for 3 h. Mild salivation and hyperventilation were observed with both doses. A short-lasting (less than 60 min) depressor response was seen with 100 micrograms/kg s.c. Prominent hyperventilation and salivation accompanied this response. A still higher dose (250 micrograms/kg s.c.) induced tremor, signs of anxiety and occasional vomiting in addition to the hyperventilation and salivation. Paradoxically, no cardiovascular activity was noted at this dose.