Central administration of a specific angiotensin II receptor antagonist on baroreflex function in spontaneously hypertensive rats.
To determine whether the increase in baroreflex sensitivity previously reported in lifetime captopril-treated spontaneously hypertensive rats (SHR) was due to an inhibition of brain angiotensin II mechanisms, we tested the effect of intracerebroventricular administration of an angiotensin II receptor antagonist on baroreflex control of heart rate in lifetime captopril-treated and untreated male and female SHR. Baroreceptor reflex control of heart rate was assessed by the slope of the relationship between changes in mean arterial pressure (delta MAP, mmHg) and changes in pulse interval (delta PI, ms). MAP was raised and lowered with infusions of phenylephrine and nitroprusside, respectively. Following basal assessment of baroreflex control of heart rate, rats received an intracerebroventricular injection (100 pmol) of Sar1Thr8 angiotensin II (sarthran) and reflex control of heart rate was reassessed. Adequacy of blockade was tested with central and peripheral administration of angiotensin II. Captopril-treated male (130 +/- 7 mmHg) and female (123 +/- 4 mmHg) rats had significantly lower MAP than untreated rats (174 +/- 4 and 173 +/- 8 mmHg, respectively) and enhanced bradycardia in response to increases in MAP. Intracerebroventricular administration of sarthran had no effect on basal blood pressure or heart rate but enhanced the bradycardia in response to increases in MAP in both untreated and captopril-treated rats. The increase in the slope of the line relating delta MAP to delta PT was greater for untreated than captopril-treated SHR (male untreated 2.7-fold versus captopril-treated 1.5-fold; female untreated 1.6-fold versus captopril-treated 1.5-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
Berecek
K H
KH
Department of Physiology and Biophysics, University of Alabama, Birmingham 35294.
Robertson
J D
JD
Thorstad
M H
MH
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001921:Brain / Q000187:drug effects; D002216:Captopril / Q000627:therapeutic use*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D011311:Pressoreceptors / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011945:Receptors, Angiotensin / Q000187:drug effects*; D012018:Reflex / Q000502:physiology; D012084:Renin-Angiotensin System / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C014805:angiotensin II, Sar(1)-Thr(8)-; D002216:Captopril