Role of nifedipine-sensitive sympathetic vasoconstriction in maintenance of high blood pressure in spontaneously hypertensive rats: effect of Gi-protein inactivation by pertussis toxin.
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.


METHODS
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).


CONCLUSIONS
The enhanced contribution of SNS to hypertension maintenance in SHRs is mediated by Gi-protein-coupled pathway controlling calcium influx through L-VDCC.
Cardiovascular Research Center and Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Mária
M
Pintérová
Petr
P
Karen
Jaroslav
J
Kunes
Josef
J
Zicha
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D020746:Calcium Channels, L-Type / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors* / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology*
D020746:Calcium Channels, L-Type; D037342:Pertussis Toxin; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D009543:Nifedipine; D009638:Norepinephrine