Strain-dependent differences of restraint stress-induced hypertension in WKY and SHR.
The aim of our study was to investigate differences in restraint stress-response between normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) and the consequences for tail-cuff (TC) blood pressure measurements. We therefore radiotelemetrically collected cardiovascular data from WKY and SHR that underwent TC procedures and measured plasma norepinephrine (NE) and angiotensin II (ATII) levels as well as gene expression of the adrenal and hypothalamic tyrosine-hydroxylase, the rate-limiting enzyme in NE synthesis. Furthermore, we determined the effects of antihypertensive therapy using the beta(1)-receptor antagonist metoprolol, the alpha(1)-receptor antagonist doxazosin and the AT(1)-receptor antagonist telmisartan as mono- or combination therapies during the TC procedure. Results show that the TC procedure induced a stress reaction characterised by greatly increasing heart rate (HR) and blood pressure (BP) and elevating plasma norepinephrine and angiotensin II concentrations. Strain-dependent differences were found concerning stress reactions during rest (more pronounced effects) and activity of the two rat strains. In both strains, metoprolol inhibited the TC-induced increase in HR and doxazosin the TC-induced increase in BP. Telmisartan, in addition, reduced hypertension in SHR, slightly reduced the TC-induced increase of BP in SHR but had no effect in WKY. The cardiovascular data as well as those on NE, ATII and TH expression clearly show that SHR are less able to cope with stress-related mechanisms than the normotensive WKY. Since TC activates both the sympathetic as well as renin-angiotensin system this method is not appropriate to evaluate neither physiological nor drug-induced effects on BP and HR.
Grundt
Alexander
A
Institute of Experimental and Clinical Pharmacology and Toxicology, Ruprecht-Karls-Universität of Heidelberg, Mannheim, Germany.
Grundt
Christina
C
Gorbey
Stefan
S
Thomas
Martin A
MA
Lemmer
Björn
B
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000209:etiology* / Q000235:genetics*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012149:Restraint, Physical / Q000009:adverse effects*; D013045:Species Specificity; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D000804:Angiotensin II; D014446:Tyrosine 3-Monooxygenase; D009638:Norepinephrine