Role of nifedipine-sensitive sympathetic vasoconstriction in maintenance of high blood pressure in spontaneously hypertensive rats: effect of Gi-protein inactivation by pertussis toxin
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Hypertension physiopathology MeSH
- Blood Pressure drug effects physiology MeSH
- Rats MeSH
- Nifedipine pharmacology MeSH
- Norepinephrine pharmacology MeSH
- Pertussis Toxin pharmacology MeSH
- Rats, Inbred SHR MeSH
- Rats, Inbred WKY MeSH
- GTP-Binding Protein alpha Subunits, Gi-Go antagonists & inhibitors physiology MeSH
- Sympathetic Nervous System drug effects physiopathology MeSH
- Calcium Signaling drug effects MeSH
- Calcium Channels, L-Type physiology MeSH
- Vasoconstriction drug effects physiology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Nifedipine MeSH
- Norepinephrine MeSH
- Pertussis Toxin MeSH
- GTP-Binding Protein alpha Subunits, Gi-Go MeSH
- Calcium Channels, L-Type MeSH
BACKGROUND: High blood pressure (BP) in spontaneously hypertensive rats (SHRs) is attributed to excessive activity of sympathetic nervous system (SNS) and relative nitric oxide deficiency. An important part of SNS hypertensive action is exerted by calcium influx through L-type of voltage-dependent calcium channels (L-VDCC). The overexpression of pertussis toxin (PTX)-sensitive inhibitory G-proteins (Gi) participating in the development and maintenance of high BP in SHRs suggested us to study Gi-protein involvement in the pathway through which noradrenergic vasoconstriction and calcium influx can be coupled. METHOD: The participation of main vasoactive systems (angiotensin II, norepinephrine, nitric oxide) in BP maintenance was investigated in conscious SHR and WKY rats (half of them being pretreated with PTX, 10 microg/kg i.v., 48 h before the experiment). To evaluate the contribution of Gi-proteins and L-VDCC to vasoconstriction induced by exogenous norepinephrine, dose-response curves were determined before and after acute nifedipine administration. RESULTS: PTX pretreatment of SHRs significantly decreased BP and reduced sympathetic vasoconstriction, which was partially substituted by enhanced angiotensin II-dependent vasoconstriction. PTX pretreatment also reduced nitric oxide-dependent vasodilation in both rat strains. PTX pretreatment of SHRs decreased BP component sensitive to acute blockade of calcium entry by nifedipine. In both strains, PTX pretreatment as well as acute nifedipine administration caused substantial rightward shift of norepinephrine dose-response curves (without additive effects of both treatments). CONCLUSION: The enhanced contribution of SNS to hypertension maintenance in SHRs is mediated by Gi-protein-coupled pathway controlling calcium influx through L-VDCC.
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
