Arterial responses in vitro and plasma digoxin immunoreactivity after losartan and enalapril treatments in experimental hypertension.
Treatment with the angiotensin-converting enzyme inhibitor, quinapril, has been shown to normalize increased dihydropyridine sensitivity and impaired potassium relaxation, characteristic features of arterial smooth muscle in spontaneously hypertensive rats, and also reduce the concentration of plasma digoxin-like immunoreactivity in these animals. However, whether angiotensin II receptor blocker therapy can beneficially influence these variables is not known. Therefore, we compared the effects of 10-week losartan and enalapril treatments (15 and 4 mg/kg/day, respectively) on functional responses of mesenteric arterial rings in spontaneously hypertensive rats and Wistar-Kyoto rats. Both losartan and enalapril normalized blood pressure, cardiac mass, and media to lumen ratio without significantly changing the media cross-sectional area in the mesenteric artery of spontaneously hypertensive rats (i.e. induced outward remodelling). The inhibitory effect of the calcium entry blocker nifedipine on calcium-evoked contractions was similar and less marked in arterial preparations from Wistar-Kyoto rats and losartan- and enalapril-treated spontaneously hypertensive rats than in those from untreated spontaneously hypertensive rats. Furthermore, the relaxations of arterial rings induced by the return of potassium to the organ bath (upon precontractions elicited by potassium-free solution) were used to evaluate the function of vascular Na+,K+-ATPase. The rate of potassium relaxation was faster in losartan- and enalapril-treated spontaneously hypertensive rats and all Wistar-Kyoto groups than in untreated spontaneously hypertensive rats, and the response was effectively inhibited by the sodium pump inhibitor ouabain. Both treatments especially augmented the ouabain-sensitive part of the potassium-relaxation in spontaneously hypertensive rats, indicating the involvement of the sodium pump in this response. However, no significant changes in plasma digoxin-like immunoreactivity were observed. In conclusion, the outward remodelling following long-term AT1-receptor blockade and angiotensin-converting enzyme inhibition in spontaneously hypertensive rats was associated with normalization of the increased dihydropyridine sensitivity of arteries. Both losartan and enalapril treatments also augmented arterial potassium relaxation in spontaneously hypertensive rats, suggesting enhanced function of Na+,K+-ATPase, but this effect could not be attributed to changes in circulating sodium pump inhibitor concentration.
Kalliovalkama
J
J
Department of Pharmacological Sciences, University of Tampere, Finland. jarkko.kalliovalkama@uta.fi
Kähönen
M
M
Tolvanen
J P
JP
Wu
X
X
Voipio
J
J
Pekki
A
A
Doris
P A
PA
Ylitalo
P
P
Pörsti
I
I
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000517:prevention & control; D004077:Digoxin / Q000097:blood* / Q000276:immunology; D004095:Dihydropyridines / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000033:anatomy & histology; D006973:Hypertension / Q000097:blood* / Q000188:drug therapy*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009543:Nifedipine / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology; D017540:Tunica Media / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004095:Dihydropyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011189:Potassium Chloride; D004656:Enalapril; D004077:Digoxin; C038806:1,4-dihydropyridine; D000254:Sodium-Potassium-Exchanging ATPase; D009543:Nifedipine; D019808:Losartan