Antihypertensive drugs: their postural hypotensive effect and their blood pressure lowering activity in conscious normotensive rats.
The postural hypotensive (PH) response to various antihypertensive agents was examined as an independent pharmacologic activity in conscious normotensive rats. Full PH dose-response curves for standard antihypertensive drugs were explored and were compared to their hypotensive dose-response curves. In untreated control rats, only a negligible change in blood pressure occurred in response to a 2 min 90 degrees head-up tilt. However, treatment with an agent acting on the nervous system, pentolinium, resulted in a profound and dose-dependent drop of blood pressure in response to tilt. A comparable hypotensive effect was also induced. Alpha blockers (e.g., prazosin) induced only moderate dose-dependent PH effects while producing profound hypotensive effects. Direct vasodilators (e.g., minoxidil), calcium antagonists (e.g., nifedipine) and a converting enzyme inhibitor, captopril, were virtually free of PH effects despite moderate or profound hypotensive effects. Clonidine exhibited greater PH than hypotensive effects. Propranolol and hydrochlorothiazide did not exhibit PH effects and did not lower blood pressure. With the exception of clonidine, these findings are generally in agreement with human data. It is suggested that the normotensive rat may be a useful model for gaining an insight into a drug's potential for producing postural hypotension in man and that the full PH dose-response curve should be explored.
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D007024:Hypotension, Orthostatic / Q000139:chemically induced*; D008297:Male; D008914:Minoxidil / Q000494:pharmacology; D009529:Nicardipine; D009543:Nifedipine / Q000031:analogs & derivatives / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010425:Pentolinium Tartrate / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D009599:Nitroprusside; D008914:Minoxidil; D010425:Pentolinium Tartrate; D002216:Captopril; D009529:Nicardipine; D009543:Nifedipine; D003000:Clonidine; D011224:Prazosin; D010646:Phentolamine